The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index; 36 of the 43 sources its claims cite were checked for support.
Social stress induces neurovascular pathology promoting depression
Open accessAbstract
Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood–brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of the endothelial cell tight junction protein claudin-5 (Cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 downregulation was sufficient to induce depression-like behaviors following subthreshold social stress whereas chronic antidepressant treatment rescued Cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or mice injected with adeno-associated virus expressing shRNA against Cldn5 caused infiltration of the peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein Cldn5, promoting peripheral IL-6 passage across the BBB and depression. Chronic social defeat stress induces loss of protein claudin-5, leading to abnormalities in blood vessel morphology, increased blood brain barrier permeability, infiltration of immune signals and depression-like behaviors.
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Written from the paper’s full text.
TL;DR
Chronic social defeat in mice reduces the endothelial tight-junction protein cldn5 in nucleus accumbens, compromises blood-brain barrier integrity, and allows circulating IL-6 to enter brain tissue, promoting depression-like behavior. Postmortem nucleus accumbens tissue from depressed patients also shows lower CLDN5 expression, linking stress-related neurovascular pathology to inflammation and depression.
Key findings
- In nucleus accumbens of stress-susceptible but not resilient mice after 10-day chronic social defeat, cldn5 mRNA and protein were reduced; normalization to endothelial marker pecam1 indicated about 40% loss (*p = 0.0009), and cldn5 levels correlated with social avoidance (p = 0.0014). Electron microscopy showed discontinuous tight junctions in susceptible mice (*p < 0.0001).
- Human postmortem nucleus accumbens CLDN5 mRNA was lower in major depressive disorder: Montreal non-medicated cases (*p = 0.0117) and Texas cases (*p = 0.0435); no significant changes were seen in hippocampus or prefrontal cortex, and cocaine users showed no change.
- Viral cldn5 knockdown in nucleus accumbens combined with subthreshold microdefeat produced depression-like behaviors: less grooming (*p = 0.0356), lower sucrose preference (p = 0.0063), more forced-swim immobility (p = 0.0015), and lower social interaction ratio (*p = 0.0386); restoring cldn5 reversed anhedonia and promoted resilience.
- Blood-brain barrier permeability increased in susceptible mice by Gd-DTPA MRI (nucleus accumbens *p = 0.0237; hippocampus p = 0.0085) and Evans blue in nucleus accumbens (p = 0.0014); IL-6 was elevated in nucleus accumbens (*p = 0.0321), biotinylated IL-6 entered nucleus accumbens parenchyma only in susceptible or cldn5-knockdown mice, and intra-nucleus accumbens IL-6 before subthreshold defeat caused social avoidance (*p = 0.0405).
Methods
- Male C57BL/6J mice underwent 10-day chronic social defeat by CD-1 aggressors and were classified as stress-susceptible or resilient by social interaction ratio (<1 vs >1); additional experiments used microdefeat, chronic variable stress, imipramine, AAV-shRNA-cldn5, tracers, MRI, transmission electron microscopy, flow cytometry, and ELISA.
- Molecular and histological work included qPCR for blood-brain barrier and cytokine genes, immunohistochemistry for cldn5/CD31, Western blot, capillary extraction, and human postmortem nucleus accumbens, hippocampus, and prefrontal cortex samples from McGill and University of Texas Southwestern cohorts.
- Analyses used t-tests, one-way and two-way ANOVA with Bonferroni post hoc tests, and Pearson correlations, with significance set at p < 0.05; quantitative assays were performed in duplicate across two cohorts.
Limitations
- The paper states that no compound currently exists to enhance Cldn5 expression, that peripheral ccr2+ monocytes were not detected infiltrating brain parenchyma unlike some prior reports, that local IL-6 production in nucleus accumbens could not be ruled out, and that human medication effects were partial or absent while most MDD subjects died by suicide.
- Evident from the text: rodent experiments used male mice only, leaving sex differences untested; human evidence is postmortem mRNA and correlational, not direct measurement of blood-brain barrier permeability or IL-6 passage in patients; the causal chain is established mainly in mouse models.
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Claims the paper makes
65 Own result · 16 Own method · 15 Own interpretation · 11 Supported · 10 Partly supported · 4 No full text of the sources · 1 Couldn’t confirm · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Individual differences in the peripheral immune system and modulation of cytokine release, notably interleukin-6 (IL-6), are associated with susceptibility versus resilience to chronic social stress11.”
§ Social stress induces neurovascular pathology promoting depression > Introduction
What the sources say
- Supportedcites [11] Hodes, G. E. et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc. Natl. Acad. Sci. USA 111, 16136–16141 (2014). source
The Results section reports that IL-6 was significantly elevated after initial social stress in mice that later developed a susceptible phenotype, compared with resilient mice. The Discussion adds that preexisting differences in peripheral immune sensitivity and IL-6 release predicted behavioral responses to subsequent social stress. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“a protocol that is insufficient to induce depression-like behaviors in male mice31”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
What the sources say
- Supportedcites [31] Hodes, G. E. et al. Sex differences in nucleus accumbens transcriptome profiles associated with susceptibility versus resilience to subchronic variable stress. J. Neurosci. 35, 16362–16376 (2015). source
Materials and Methods specifies that the SCVS protocol lasted six days. In “Female but not male mice are susceptible to SCVS,” the paper reports that males subjected to the same protocol showed none of the measured depression-like behavioral abnormalities. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder.”
- Also stated in: § Introduction · plain
“clinical studies report higher levels of circulating pro-inflammatory cytokines in MDD patients, a pattern that has been replicated in preclinical animal models of depression1, 7–10.”
§ Social stress induces neurovascular pathology promoting depression > Abstract
What the sources say
- Supportedcites [1] Ménard, C., Pfau, M. L., Hodes, G. E. & Russo, S. J. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology 42, 62–80 (2017). source
The “Peripheral cytokines and depression” section describes a potential causal link between inflammation and MDD and reports higher circulating pro-inflammatory cytokines in depressed individuals. The Introduction also describes a theory in which excess cytokine secretion contributes to depression-related disruptions. These passages support the citing sentence’s qualified wording, “Studies suggest.” Page numbers are not available in our copy. (LLM, conf=0.88)
- Supportedcites [7] Hodes, G. E., Kana, V., Menard, C., Merad, M. & Russo, S. J. Neuroimmune mechanisms of depression. Nat. Neurosci. 18, 1386–1393 (2015). source
In the opening section (page not provided), the authors state that they regard inflammation as a contributing factor to mood disorders. In “The immune system and major depressive disorder,” they report elevated circulating inflammatory markers in patients with MDD and evidence that peripheral inflammation can precede its onset. This supports the citing sentence’s qualified wording, “Studies suggest.” (LLM, conf=0.92)
- Supportedcites [8] Barnes, J., Mondelli, V. & Pariante, C. M. Genetic contributions of inflammation to depression. Neuropsychopharmacology 42, 81–98 (2017). source
The Introduction reports elevated inflammatory markers in the peripheral blood of patients with major depression and states that administering cytokines can cause depression. This supports the hedged claim that peripheral inflammation contributes to its development; the Concluding Remarks qualify that raised inflammatory markers occur in only a subset of depressed patients. (LLM, conf=0.89)
- Supportedcites [9] Dantzer, R. Cytokine, sickness behavior, and depression. Immunol. Allergy Clin. North Am. 29, 247–264 (2009). source
The “Pathophysiologic implications” section (page not provided) reports elevated circulating proinflammatory cytokines in major depression and says chronic activation of the innate immune system can precipitate depressive disorders. That supports the citing sentence’s qualified claim that heightened peripheral inflammation contributes to depression. (LLM, conf=0.90)
- Supportedcites [10] Miller, A. H. & Raison, C. L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16, 22–34 (2016). source
The “Inflammation and depression” section reports elevated inflammatory markers in patients with major depressive disorder and says that administering inflammatory cytokines or their inducers can cause depressive symptoms. The paper also describes mechanisms through which inflammation may contribute to depression. This supports the citing sentence’s hedged claim, without implying that inflammation contributes to every case. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Introduction · plain
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chronic antidepressant treatment can reverse CSDS-induced depression-like behaviors, including social avoidance25, 32.”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
What the sources say
- Not checked — no full text of the sourcecites [25] Berton, O. & Nestler, E. J. New approaches to antidepressant drug discovery: beyond monoamines. Nat. Rev. Neurosci. 7, 137–151 (2006). source
- Partly supportedcites [32] Golden, S. A. et al. Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat. Med. 19, 337–344 (2013). sourceExperimental — accuracy not yet measured
The Results section on stress-induced Rac1 regulation reports that 35 days of imipramine treatment partially reversed social avoidance in mice after chronic social defeat. It does not establish reversal of other depression-like behaviors by that treatment, and the claim omits the qualification that the observed reversal was partial. Page numbers are unavailable in our copy. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“We previously reported a 27-fold increase in circulating IL-6 level 20-min after defeat in SS mice11.”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
What the sources say
- Supportedcites [11] Hodes, G. E. et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc. Natl. Acad. Sci. USA 111, 16136–16141 (2014). source
The Results describe cytokine measurements 20 minutes after the first defeat and report elevated IL-6 in mice that later developed a susceptible phenotype. The passage accompanying the time-course analysis identifies a 27-fold change in IL-6 in susceptible animals and confirms elevated circulating IL-6 within 20 minutes of defeat. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“injection of AAV-shRNA-cldn5 enhances passive diffusion of Gd-DTPA from the blood into the brain33”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
What the sources say
- Partly supportedcites [33] Campbell, M. et al. Systemic low-molecular weight drug delivery to pre-selected neuronal regions. EMBO Mol. Med. 3, 235–245 (2011). sourceExperimental — accuracy not yet measured
The Results section (“Systemic and stereotaxic injection of CLDN5 AAV-2/9”) reports enhanced passive diffusion of Gd-DTPA from blood to brain after injection in mice. However, the effect was induced with doxycycline; the paper says no barrier permeability was observed after doxycycline was removed, a necessary condition omitted from the claim. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We nevertheless confirm a recent report showing that monocytes are recruited to vessels and ventricular space within the brain34.”
§ Social stress induces neurovascular pathology promoting depression > Discussion
What the sources say
- Partly supportedcites [34] McKim, D.B. et al. Microglial recruitment of IL-1β-producing monocytes to brain endothelium causes stress-induced anxiety. Mol. Psychiatry https://doi.org/10.1038/mp.2017.64 (2017). sourceExperimental — accuracy not yet measured
The Results section (‘Threat appraisal during stress promotes microglial activation and monocyte recruitment’; page unavailable) reports that stress increased monocyte adhesion to brain endothelial cells, supporting recruitment to vessels. Our copy does not report recruitment to the ventricular space; searches for ventricular space, ventricles, and choroid plexus found no such passage. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“To our knowledge, this is the first study to provide direct evidence that chronic stress is sufficient to allow infiltration of circulating cytokines in the absence of local mechanical trauma or a brain tumor41, 42.”
§ Social stress induces neurovascular pathology promoting depression > Discussion
What the sources say
- Could not verifycites [41] Coppen, A. J. Abnormality of the blood-cerebrospinal fluid barrier of patients suffering from a depressive illness. J. Neurol. Neurosurg. Psychiatry 23, 156–161 (1960). sourceExperimental — accuracy not yet measured
The Summary (page not provided) reports reduced entry of radioactive sodium into cerebrospinal fluid in patients with depressive illness, not infiltration of circulating cytokines. Searches for chronic stress, cytokines, mechanical trauma, and brain tumors found no passage addressing the attributed claim. (LLM, conf=0.76)
- Partly supportedcites [42] Hambardzumyan, D., Gutmann, D. H. & Kettenmann, H. The role of microglia and macrophages in glioma maintenance and progression. Nat. Neurosci. 19, 20–27 (2016). sourceExperimental — accuracy not yet measured
The ‘Origins of glioma associated microglia and macrophages’ section (page unavailable) discusses infiltration of blood-derived monocytes into the diseased CNS, and ‘TAM recruitment’ describes macrophages accumulating around gliomas. This supports the brain-tumor comparison, but the paper does not report infiltration of circulating cytokines or show that chronic stress is sufficient to cause it. The ‘first study’ characterization is the citing authors’ own conclusion. (LLM, conf=0.82)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We previously reported higher serum IL-6 in untreated patients with MDD and treatment-resistant MDD when compared to healthy controls11.”
§ Social stress induces neurovascular pathology promoting depression > Discussion
What the sources say
- Partly supportedcites [11] Hodes, G. E. et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc. Natl. Acad. Sci. USA 111, 16136–16141 (2014). sourceExperimental — accuracy not yet measured
The Significance passage and Fig. 1C report higher serum IL-6 in patients with treatment-resistant MDD than in healthy controls. The paper describes both patient cohorts as treatment-resistant; the Materials and Methods passage does not establish a separate untreated MDD group or specify that the patients were untreated at sampling. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“cldn5-deficient mice die within 10 h of birth23”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
What the sources say
- Supportedcites [23] Nitta, T. et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 161, 653–660 (2003). source
The Results section (‘Generation of Cld-5–deficient mice’) states that the homozygous Cld5−/− mice all died within 10 hours of birth. Figure 1’s caption reports the same finding. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
- It may state two separate claims as one. 28
- Probably not a substantial claim. 27
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Chronic stress mobilizes the innate immune system and stimulates enhanced proliferation and release of inflammatory monocytes and neutrophils into the bloodstream12, 13.”
§ Social stress induces neurovascular pathology promoting depression > Introduction
What the sources say
- Partly supportedcites [12] Powell, N. D. et al. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc. Natl. Acad. Sci. USA 110, 16574–16579 (2013). sourceExperimental — accuracy not yet measured
The Mouse Monocyte Subset Differentiation section (page not available) reports increased proinflammatory monocytes and granulocytes in the blood and bone marrow after repeated social defeat; the mouse myeloid-lineage analysis also reports increased progenitors of both types. The paper does not identify the granulocytes specifically as neutrophils or directly measure their release into the bloodstream, and its human analysis concerns monocytes rather than neutrophils. (LLM, conf=0.84)
- Supportedcites [13] Heidt, T. et al. Chronic variable stress activates hematopoietic stem cells. Nat. Med. 20, 754–758 (2014). source
The passages labeled Abstract report that chronic stress increases hematopoietic stem-cell proliferation, raising the output of inflammatory monocytes and neutrophils. They also describe extensive release of inflammatory leukocytes into circulation in stressed mice. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“loss of Cldn5 has been shown to promote loosening of the BBB and increased permeability23.”
§ Social stress induces neurovascular pathology promoting depression > Introduction
What the sources say
- Supportedcites [23] Nitta, T. et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 161, 653–660 (2003). source
The Introduction states that the BBB was loosened in Cld-5–deficient mice. The Results section, “Size-selective loosening of the BBB in Cld-5–deficient mice,” reports that a tracer excluded from wild-type brains leaked into the brain tissue of deficient mice, demonstrating increased permeability. The loosening was size-selective, not permeability to all substances. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“clinical studies report higher levels of circulating pro-inflammatory cytokines in MDD patients, a pattern that has been replicated in preclinical animal models of depression1, 7–10.”
§ Social stress induces neurovascular pathology promoting depression > Introduction
What the sources say
- Supportedcites [1] Ménard, C., Pfau, M. L., Hodes, G. E. & Russo, S. J. Immune and neuroendocrine mechanisms of stress vulnerability and resilience. Neuropsychopharmacology 42, 62–80 (2017). source
The “Peripheral cytokines and depression” section (page not provided) reports clinical evidence that depressed individuals have higher circulating levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNFα. It also reports increased pro-inflammatory cytokines in rodent models of depression-like behavior. (LLM, conf=0.94)
- Supportedcites [7] Hodes, G. E., Kana, V., Menard, C., Merad, M. & Russo, S. J. Neuroimmune mechanisms of depression. Nat. Neurosci. 18, 1386–1393 (2015). source
The section “The immune system and major depressive disorder” reports elevated circulating pro-inflammatory cytokines in patients with depression. Table 1, “Cytokine profiles for animal models of depression,” lists increased peripheral cytokines in several stress-based animal models. The paper qualifies the clinical finding as occurring in subsets of patients, not necessarily all patients with MDD. (LLM, conf=0.91)
- Partly supportedcites [8] Barnes, J., Mondelli, V. & Pariante, C. M. Genetic contributions of inflammation to depression. Neuropsychopharmacology 42, 81–98 (2017). sourceExperimental — accuracy not yet measured
The Introduction (page not provided) reports increased inflammatory cytokines in the peripheral blood of some patients with major depression, supporting the clinical portion. The Materials and methods section (page not provided) says papers concerning animal models were excluded, so this source does not support the claimed replication in preclinical animal models. (LLM, conf=0.90)
- Partly supportedcites [9] Dantzer, R. Cytokine, sickness behavior, and depression. Immunol. Allergy Clin. North Am. 29, 247–264 (2009). sourceExperimental — accuracy not yet measured
The Pathophysiologic implications section reports elevated circulating proinflammatory cytokines, particularly IL-6, in major depression. It also describes depressive-like behavior in mice subjected to inflammation, but does not say that elevated circulating cytokine levels in depressed patients were replicated in animal models. Page numbers were not available in our copy. (LLM, conf=0.86)
- Partly supportedcites [10] Miller, A. H. & Raison, C. L. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16, 22–34 (2016). sourceExperimental — accuracy not yet measured
The “Inflammation and depression” section reports increased pro-inflammatory cytokine expression in patients with major depressive disorder and identifies peripheral-blood IL-1β, IL-6 and TNF as reliable inflammatory biomarkers. The “Risk and resilience” section describes mice whose blood leukocytes produced more IL-6 ex vivo and were more susceptible to stress-induced depressive-like behaviour, but it does not report that the mice had higher circulating cytokine levels. Thus, the claimed replication of the circulating-cytokine pattern in animal models is not established by this copy. (LLM, conf=0.84)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Cldn5 is an endothelial cell-specific tight junction protein (Supplementary Fig. 2D)29, 30, which we confirmed to be enriched in blood vessels using a brain capillary extraction method”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
What the sources say
- Partly supportedcites [29] Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J. Neurosci. 34, 11929–11947 (2014). sourceExperimental — accuracy not yet measured
The section “RNA-Seq analysis identifies novel cell type-enriched genes” identifies Cldn5 as an endothelial-cell-specific marker, supporting that part of the cited description. The passages do not identify it as a tight junction protein. Enrichment in extracted blood vessels is presented in the citing sentence as the citing authors’ own confirmation, not a finding attributed to this source. (LLM, conf=0.86)
- Partly supportedcites [30] Zhang, Y. et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron 89, 37–53 (2016). sourceExperimental — accuracy not yet measured
The Results section on purified human cell transcriptomes identifies CLDN5 as an endothelial cell-specific marker and reports selective expression in endothelial cells. Our copy does not identify CLDN5 as a tight junction protein. The blood-vessel enrichment is presented in the citing sentence as the citing authors’ own confirmation, not a finding attributed to this source. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The NAc plays a crucial role in stress responses and mood disorders including MDD28.”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
What the sources say
- Supportedcites [28] Russo, S. J. & Nestler, E. J. The brain reward circuitry in mood disorders. Nat. Rev. Neurosci. 14, 609–625 (2013). source
The section on structural and functional synaptic plasticity reports stress-induced changes in the NAc in mice and decreased NAc responses in patients with depression. The section on transcriptional mechanisms also links NAc activity to stress susceptibility and depression-like behavior. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Without the introduction of pro-depressive manipulations, this protocol is insufficient to induce depression-like behaviors and thus can be used to identify pro-susceptibility factors32.”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
What the sources say
- Supportedcites [32] Golden, S. A. et al. Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat. Med. 19, 337–344 (2013). source
The Results section, under “Rac1 modulates depression-related behavior,” states that subthreshold microdefeats do not produce social avoidance or anhedonia in control mice and can therefore reveal pro-susceptibility factors. This supports the claim about the protocol without pro-depressive manipulations. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Sample size for CSDS mouse cohorts was calculated based on previous studies of CSDS and depression-like behaviors11, 32”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
What the sources say
- Supportedcites [11] Hodes, G. E. et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc. Natl. Acad. Sci. USA 111, 16136–16141 (2014). source
The paper is a previous mouse study of repeated social defeat stress and depression-like behavior, so it fits the cited role of a prior study used to inform cohort size. Its Results (Fig. 2 caption; page unavailable) report group sizes for mice assessed after stress. The claim concerns how the citing authors chose their sample size, not whether this source performed a sample-size calculation. (LLM, conf=0.86)
- Supportedcites [32] Golden, S. A. et al. Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat. Med. 19, 337–344 (2013). source
The Results section (page unavailable) describes this paper's chronic social defeat stress mouse cohorts and their depression-like behaviors, including social avoidance and anhedonia. The citation identifies a previous study relevant to the citing authors' sample-size planning; it does not attribute their calculation to this paper. (LLM, conf=0.87)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Previous studies report conflicting findings with regard to infiltration of peripheral immune cells into the brain following social stress14, 34.”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
What the sources say
- Partly supportedcites [14] Wohleb, E. S., Powell, N. D., Godbout, J. P. & Sheridan, J. F. Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes anxiety-like behavior. J. Neurosci. 33, 13820–13833 (2013). sourceExperimental — accuracy not yet measured
The Results report that repeated social defeat caused peripheral macrophages to infiltrate specific brain regions, supporting one side of the cited comparison. The Discussion also contrasts this finding with earlier work focused on resident microglia, but the passages do not establish that previous studies reported conflicting findings about whether peripheral cells infiltrate the brain. No page number was available in our copy. (LLM, conf=0.83)
- Partly supportedcites [34] McKim, D.B. et al. Microglial recruitment of IL-1β-producing monocytes to brain endothelium causes stress-induced anxiety. Mol. Psychiatry https://doi.org/10.1038/mp.2017.64 (2017). sourceExperimental — accuracy not yet measured
The Results section reports that repeated social defeat increased monocyte adhesion to brain endothelial cells, supporting one finding about peripheral immune-cell recruitment after social stress. The paper does not report conflicting findings across studies, and endothelial adhesion does not by itself establish infiltration into brain tissue. No page number is available in our copy. (LLM, conf=0.82)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We took advantage of ccr2RFP∷ cx3cr1GFP double heterozygous mice 35 in which adult resident microglia exhibit a ccr2RFP−/cx3cr1GFP+ pattern35, 36, whereas peripheral monocytes, which are recruited in response to inflammation, are characterized by a ccr2RFP+/cx3cr1GFP− pattern35–37.”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
What the sources say
- Partly supportedcites [35] Saederup, N. et al. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS One 5, e13693 (2010). sourceExperimental — accuracy not yet measured
The Discussion identifies resident microglia as GFP-only and infiltrating monocyte-derived cells as RFP-positive. It does not characterize the recruited monocytes as uniformly GFP-negative: the Discussion says they have varying degrees of GFP expression, and the Results report RFP/GFP double-positive monocytes entering inflamed brain tissue. (LLM, conf=0.90)
- Partly supportedcites [36] Mizutani, M. et al. The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J. Immunol. 188, 29–36 (2012). sourceExperimental — accuracy not yet measured
The Results section reports that resident microglia are CX3CR1-GFP positive and CCR2-RFP negative in the double-heterozygous mice, including during inflammation. It describes classical infiltrating monocytes as CCR2 positive but CX3CR1 low or negative—not uniformly negative. The Introduction also describes a CX3CR1-high, CCR2-low infiltrating monocyte population, so the claimed pattern is too categorical for recruited peripheral monocytes. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [37] Ginhoux, F. & Jung, S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat. Rev. Immunol. 14, 392–404 (2014). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“While size-selective loosening of the BBB to small molecules (< 800 Da) was previously described in cldn5-deficient mice23”
§ Social stress induces neurovascular pathology promoting depression > Discussion
What the sources say
- Supportedcites [23] Nitta, T. et al. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 161, 653–660 (2003). source
The Discussion states that the BBB in claudin-5–deficient mice was affected for small molecules below approximately 800 Da, but not larger molecules. It cautions that the cutoff is tentative because the tracers differed in chemical properties; the citing sentence's rounded threshold is a fair paraphrase. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“No difference in basal IL-6 was observed before stress and IL-6 remained elevated in SS mice 48h after the last defeat11.”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
What the sources say
- Supportedcites [11] Hodes, G. E. et al. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc. Natl. Acad. Sci. USA 111, 16136–16141 (2014). source
The time-course passage (labeled Significance) reports no basal IL-6 differences before repeated social defeat stress (RSDS) and significantly elevated IL-6 in susceptible mice 48 hours after the last defeat. The Fig. 1A caption in the same section confirms both findings relative to resilient and control mice. (LLM, conf=0.95)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Cohorts were matched as closely as possible for gender, age, race, pH, postmortem interval and RNA integrity number32.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Human postmortem tissue collection
What the sources say
- Could not verifycites [32] Golden, S. A. et al. Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression. Nat. Med. 19, 337–344 (2013). sourceExperimental — accuracy not yet measured
The Results section on MDD subjects describes two postmortem cohorts and refers to supplemental demographic tables, but the passages in our copy do not say the cohorts were matched on the listed characteristics. Searches for matching, postmortem interval, RNA integrity number, and the other specified characteristics did not locate that assertion. (LLM, conf=0.72)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the Texas cohort, CLDN5 mRNA level was significantly reduced between MDD patients and healthy controls (*p = 0.0435) with no effect of medication”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Ultrastructural abnormalities were present in both large vessels and capillaries of the NAc”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“acute imipramine injection was not sufficient to alter cldn5 mRNA (Supplementary Fig. 5E) or social avoidance32”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The dye seemed to accumulate in the perivascular space of NAc blood vessels but not within the brain parenchyma”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Evans blue cannot readily cross the BBB in the absence of neurovascular damage.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Injection of AAV-sRNA-cldn5 and AAV-shRNA viruses in the HIPP (Supplementary Fig. 7A–B) had no effect on grooming in the splash test or sucrose preference”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our studies also revealed that the NAc is largely impermeable to circulating IL-6 under normal conditions as we were unable to detect biotinalyted-IL6 in the NAc of unstressed CTRL mice (Fig. 4G) and i.p. injections of recombinant IL-6 did not increase levels of IL-6 in NAc of naive mice (Fig. 4E) despite there being a large increase in the blood of these mice”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The biotinylated IL-6 signal detected in the NAc parenchyma reflects passage of peripheral IL-6 rather than local production or altered trafficking due to tagging.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“stressed AAV-shRNA-cldn5 mice in the second cohort remaining on doxycycline (Supplementary Fig. 7G) displayed anhedonia, social avoidance (Supplementary Fig. 7K) and lower cldn5 mRNA and protein levels”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“further analysis by IHC revealed that peripheral monocytes accumulate within ventricular space and NAc blood vessels, but do not infiltrate the brain parenchyma”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No change was observed for other claudins or markers of endothelial cells, pericytes, astrocytes and microglia (Supplementary Fig. 6A, qPCR primers are listed in Supplementary Information Table 4) or protein level of endothelial cell marker CD31”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Recovery of normal cldn5 expression reversed anhedonia and promoted resilience in the social interaction test in stressed AAV-shRNA-cldn5 mice”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“biotinylated-IL6 was only detectable in the NAc of SS mice and labeling with the perivascular marker CD31 revealed passage outside of blood vessels into the parenchyma”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The biotinylated IL-6 signal detected in the NAc parenchyma reflects passage of peripheral IL-6 rather than local production or altered trafficking due to tagging.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They also displayed greater social avoidance when compared to unstressed controls and stressed AAV-shRNA mice as measured by lower social interaction ratio (*p = 0.0386)”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lack of significant medication effects may be related to suicide as cause of death for the majority of MDD patients in our cohorts.”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“loss of CLDN5 may be at least partly specific to mood disorders as no change was observed in postmortem NAc tissue from cocaine users when compared to healthy controls”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“cldn5 downregulation by stress does not occur ubiquitously throughout the brain and therefore likely plays a specialized role in depression-like symptomatology”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Similarly, in rodents, CSDS induces a depression-like phenotype (social avoidance, anhedonia) in a subset of mice termed stress-susceptible (SS) that can be reversed only by chronic, but not acute, antidepressant treatment25, 26.”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
What the sources say
- Not checked — no full text of the sourcecites [25] Berton, O. & Nestler, E. J. New approaches to antidepressant drug discovery: beyond monoamines. Nat. Rev. Neurosci. 7, 137–151 (2006). source
- Not checked — no full text of the sourcecites [26] Ménard, C., Hodes, G. E. & Russo, S. J. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience 321, 138–162 (2016). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Cldn5 is a major cell adhesion molecule of endothelial cells22”
§ Social stress induces neurovascular pathology promoting depression > Introduction
What the sources say
- Not checked — no full text of the sourcecites [22] Günzel, D. & Yu, A. S. Claudins and the modulation of tight junction permeability. Physiol. Rev. 93, 525–569 (2013). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Chronic social stress is a prominent contributor to mood disorder prevalence and suicide attempts in victims of bullying24.”
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
What the sources say
- Not checked — no full text of the sourcecites [24] Meltzer, H., Vostanis, P., Ford, T., Bebbington, P. & Dennis, M. S. Victims of bullying in childhood and suicide attempts in adulthood. Eur. Psychiatry 26, 498–503 (2011). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, our findings suggest that chronic social stress alters BBB integrity through downregulation of the tight junction protein cldn5 in the NAc which, combined with stress-induced recruitment of peripheral immune signals, results in increased BBB permeability and passage of blood circulating proteins such as IL-6 and the development of depression-like behaviors”
§ Social stress induces neurovascular pathology promoting depression > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Evans blue cannot readily cross the BBB in the absence of neurovascular damage.
- Rests on an assumption: The biotinylated IL-6 signal detected in the NAc parenchyma reflects passage of peripheral IL-6 rather than local production or altered trafficking due to tagging.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Together, these observations indicate that BBB integrity is impaired in SS, but not RES mice, in line with a loss of Cldn5 and abnormal blood vessel ultrastructure.”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Evans blue cannot readily cross the BBB in the absence of neurovascular damage.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings suggest that cldn5 expression plays a protective role in behavioral response to social stress, possibly by maintaining BBB impermeability to stress-induced passage of peripheral immune signals.”
§ Social stress induces neurovascular pathology promoting depression > Results > Downregulation of cldn5 expression induces depression-like behaviors
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All mouse procedures were performed in accordance with the National Institutes of Health Guide for Care and Use of Laboratory Animals and the ISMMS Animal Care and Use Committee.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Mice
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations indicate that social stress causes direct passage of the pro-inflammatory cytokine IL-6, which then acts directly within the NAc to induce depression-like behaviors.”
§ Social stress induces neurovascular pathology promoting depression > Results > Chronic social stress alters blood vessel ultrastructure, promoting blood-brain barrier leakiness and passage of peripheral signals into the brain
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: The biotinylated IL-6 signal detected in the NAc parenchyma reflects passage of peripheral IL-6 rather than local production or altered trafficking due to tagging.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Subjects with knock history of neurological disorders or head injury were also excluded.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Human postmortem tissue collection
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Placement was validated with visualization of blood vessels with EB, green fluorescent protein (gfp) and cldn5 IHC.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Stereotaxic surgery and viral gene transfer
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A kidney lysate was used as a positive control.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Detection of injected tracers
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All blood vessels on the sample were imaged at a low and high magnification, with a total minimum of 100 images per animal (grid) sampled.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Transmission electron microscopy (TEM)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Outliers for social interaction (SI) test screening were identified as being greater than two standard deviations from the mean and excluded.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Dead cells and doublets were excluded from all analysis.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Isolation of brain leukocytes and flow cytometry
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Clinical records and interviews were obtained for each case and reviewed by three to four mental health professionals to establish independent diagnoses followed by a consensus diagnosis in line with the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Human postmortem tissue collection
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Blood toxicology was performed to exclude subjects using illicit drugs or psychotropic medications.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Human postmortem tissue collection
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“One unstressed AAV-shRNA-cldn5 mouse was excluded after verification of virus injection placement.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All mice were assigned to stress-susceptible (SS) or resilient (RES) groups based on their behavioral profile when compared to unstressed controls (CTRL).”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“If not, scoring was done by experimenters blinded to experimental conditions (for splash test, sucrose preference test and forced swim test).”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All quantitative PCR, immunohistochemistry and BBB-related tracer quantification were performed in duplicate in two different cohorts of mice.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“SI screening and behavioral tests were performed with automated tracking systems when possible.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Outliers for behavioral testing, for example characterized by impaired locomotion, were identified as being greater than two standard deviations from the mean and excluded from statistical analysis.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“CTRL and SS mice were randomly assigned to vehicle or imipramine treatment groups using Excel spreadsheet random function.”
- Also stated in: § Imipramine treatment · plain
“Following SI test, unstressed CTRL and SS mice were randomly divided into either vehicle or imipramine treatment groups.”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Statistical analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Also stated in: § Imipramine treatment · plain
The paper relies on this without support.
Evans blue cannot readily cross the BBB in the absence of neurovascular damage.
“which cannot readily cross the BBB in the absence of neurovascular damage”
The paper relies on this without support.
The biotinylated IL-6 signal detected in the NAc parenchyma reflects passage of peripheral IL-6 rather than local production or altered trafficking due to tagging.
“we tagged mouse recombinant IL-6 with biotin (~0.45 kDa) and injected it retro-orbitally into the blood of CTRL, SS or RES mice”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Stress-linked psychiatric disorders, including anxiety and major depressive disorder, are associated with systemic inflammation.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Mechanistically, social defeat stress upregulates inflammatory TNF and/or nuclear factor-κB (NFКB) signaling pathways in endothelial cells and diminishes expression of the tight junction protein claudin-5 (CLDN5)7,74.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This allows pro-inflammatory leukocytes, or their secreted factors (such as IL6 or matrix metalloproteinase-8), to enter the brain parenchyma where they impact neuronal excitability7,75,76 (Fig. 3).”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Our previous findings and those of others indicate that the severity of depression is associated with the secretion level of circulating cytokines and chemokines, which compromise the blood–brain barrier (BBB) and then activate central immune responses [10–13].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [11]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Proinflammatory cytokine mediated disruption of the BBB is the primary link connecting peripheral and neuroinflammation (81).”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [81]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As a pro-inflammatory cytokine, the increase in IL-6 levels within the central nervous system may also be associated with reduced synthesis of endothelial tight junction proteins, such as claudin-5 and occludin [21,22], which compromises the integrity of the blood–brain barrier. This, in turn, contributes to various psychological abnormalities or disorders, such as depression and anxiety.”
From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [22]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“It is becoming increasingly recognized that individuals with stress-related disorders, such as major depressive disorder (MDD), exhibit signs of chronic low-grade systemic inflammation.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [7]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Chronic administration of imipramine normalized claudin-5 mRNA expression in the nucleus accumbens and reversed depressive behaviors in stress susceptible mice (81).”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“Abundant experimental evidence suggests that the BBB is compromised after repeated stress exposure [11, 38, 39].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“The infiltration of peripheral IL-6 into the brain parenchyma led to the development of depression-like behaviors.”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [81]
The cited source says what the claim attributes to it.
In the citing paper
“Menard and colleagues found reduced expression of claudin-5, an endothelial cell tight junction protein, and abnormal blood vessel morphology in the nucleus accumbens promoted the passage of IL-6 across the BBB.”
From Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories (2023) · cites this paper as [81]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Consequently, it is hypothesized that HPA axis hyperactivity and resulting GC resistance may represent a connection between chronic stress and a major depressive disorder [101,102].”
From The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders (2023) · cites this paper as [102]
Experimental — accuracy not yet measuredIn the citing paper
“A risk factor like acute or chronic stress could, for example, lead to an increased production of pro-inflammatory cytokines (115, 138–140)”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [139]
In the citing paper
“Furthermore, neurovascular damage induced by the peripheral myeloid cells, pro-inflammatory cytokines, and the dysregulation of the complement pathways could be a further potential mechanism of action [36,37,38].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [36]
In the citing paper
“For instance, it has been suggested that an increase of the blood-brain barrier (BBB) permeability could be determined by severe stress and/or traumatic brain injury [35,36].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [36]
In the citing paper
“Interestingly, chronic stress itself can also lead to BBB dysfunction in the nucleus accumbens to promote depressive-like behaviors in mice, changes linked to increased monocyte accumulation and reduced neuronal cAMP production [167].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [167]
In the citing paper
“Chronic stress also increases the leakiness of the blood-brain barrier to permit infiltration of peripheral immune cells and cytokines such as IL-6 [184].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [184]
In the citing paper
“A recent study indicated that peripheral IL-6 may directly enter the brain via increased blood-brain barrier permeability and promote social avoidance following social defeat stress [20].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [20]
In the citing paper
“Recent studies modeling social stress in mice indicate that peripheral IL-6 can enter the brain and influence the social avoidance response [20].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Social stress induces neurovascular pathology promoting depression > Results > Vulnerability to chronic social stress and MDD are associated with loss of tight junction protein cldn5 expression
“About half of the MDD subjects in each cohort were on medication at time of death as determined by toxicology reports (Supplementary Information Table 2–3).”
§ Social stress induces neurovascular pathology promoting depression > Online Methods > Human postmortem tissue collection
“Blood toxicology was performed to exclude subjects using illicit drugs or psychotropic medications.”
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Metadata
- Authors
- Menard, C., Pfau, M. L., Hodes, G. E., Kana, V., Wang, V. X., Bouchard, S., Takahashi, A., Flanigan, M. E., Aleyasin, H., LeClair, K. B., Janssen, W. G., Labonté, B., Parise, E. M., Lorsch, Z. S., Golden, S. A., Heshmati, M., Tamminga, C., Turecki, G., Campbell, M., Fayad, Z. A., Tang, C. Y., Merad, M., & Russo, S. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Tisch Cancer Institute (US)
- University of Tsukuba (JP)
- The University of Texas Southwestern Medical Center (US)
- Douglas Mental Health University Institute (CA)
- Trinity College Dublin (IE)
- Corresponding author
- Russo, Scott J.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2017-11-13
- Volume
- 20
- Issue
- 12
- Pages
- 1752-1760
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC5726568
- OpenAlex
- W2767440265
- Semantic Scholar
- 66079f02fd3a498f89804c77717db403860e60a8
- Cited by
- 1,028
- References
- 53
- Citations by year
- 2026: 132 · 2025: 152 · 2024: 147 · 2023: 122 · 2022: 137 · 2021: 110 · 2020: 90 · 2019: 80 · 2018: 50 · 2017: 5
- FWCI
- 30.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Sunderland Repository (University of Sunderland) (submittedVersion)
- Funders
- Health Research Board (HRA-POR-2015-1077)
- Japan Society for the Promotion of Science (17H04766, 15K12773)
- National Institute of Mental Health (F31MH105217, F30MH100835, R01MH090264, F30MH110073, P50MH096890, T32MH096678, R01MH114882, F31MH111108, R01MH104559, T32MH087004)
- National Center for Complementary and Integrative Health (P50AT008661)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- chronic social defeat stress, major depressive disorder, blood-brain barrier permeability, claudin-5, tight junctions, nucleus accumbens, peripheral inflammation, interleukin-6, antidepressant treatment, stress resilience, neurovascular pathology
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Blood-Brain Barrier, Depression, Feeding Behavior, Food Preferences, Imipramine, Male, Mice, Inbred C57BL, Nucleus Accumbens, Social Environment, Stress, Psychological, Swimming, Interleukin-6, Adrenergic Uptake Inhibitors, Mice, Claudin-5, Tight Junction Proteins
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