The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus
Open accessAbstract
Regulation of the hypothalamic–pituitary–adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased expression of the glucocorticoid receptor (GR) has been documented. To investigate the role of the GR in CRH neurons, we have targeted the deletion of the GR, specifically in the parventricular nucleus. Impairment of GR function in the parventricular nucleus resulted in an enhancement of CRH expression and an up-regulation of hypothalamic levels of BDNF and disinhibition of the HPA axis. BDNF is a stress and activity-dependent factor involved in many activities modulated by the HPA axis. Significantly, ectopic expression of BDNF in vivo increased CRH, whereas reduced expression of BDNF, or its receptor TrkB, decreased CRH expression and normal HPA functions. We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Additional evidence for CORT acting directly on PVN neurons comes from studies where targeted deletion of GR in the PVN increased CRH expression and CORT and ACTH levels in male mice (Jeanneteau et al., 2012).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Jeanneteau et al., 2012
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 cross-talk between BDNF and CRH may be at least partly mediated by the CREB and MAPK pathway and is involved in the enhancement of fear memory under stress (187).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
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
“The administration of BDNF in vivo induces increased CRH level and reduction of BDNF or its receptor normalizes the CRH level and thus, the HPA axis.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Moreover, there is a feedback loop whereby directly regulates CRH, and thus, the HPA axis (187).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
The cited source says what the claim attributes to it.
In the citing paper
“For BDNF, its expression level responds to stress-related HPA axis activation.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
The cited source says what the claim attributes to it.
In the citing paper
“BDNF directly regulates the HPA axis.”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [187]
In the citing paper
“Finally, the broad disruption of the GR allele in the CNS [GRNesCre (5)] and its targeted deletion in the forebrain [forebrain-specific GR knock-out; FBGRKO mice] (119), or the PVN all resulted in the disinhibition of the HPA axis (120).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [120]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 5,429 · cited 3×
“When compromised, the HPA axis is not able to adequately respond to external stressors, and many maladaptative changes may occur that can set the stage for neuropsychiatric disorders (3).”
BackgroundStress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621
CREB: A Stimulus-Induced Transcription Factor Activated by A Diverse Array of Extracellular Signals
Shaywitz, A. J., & Greenberg, M. E. (1999) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.68.1.821 · Cited by 2,133
Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety
Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., & Schütz, G. (1999) · Nature Genetics · doi:10.1038/12703 · Cited by 1,841
Neurotrophins as synaptic modulators
Poo, M.-M. (2001) · Nature Reviews Neuroscience · doi:10.1038/35049004 · Cited by 1,775
Limbic system mechanisms of stress regulation: Hypothalamo-pituitary-adrenocortical axis
Herman, J. P., Ostrander, M. M., Mueller, N. K., & Figueiredo, H. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2005.08.006 · Cited by 1,322
New insights into BDNF function in depression and anxiety
Martinowich, K., Manji, H., & Lu, B. (2007) · Nature Neuroscience · doi:10.1038/nn1971 · Cited by 1,221
Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure
Balthasar, N., Dalgaard, L. T., Lee, C. E., Yu, J. H., Funahashi, H., Williams, T. B., Ferreira, M. A. R., Tang, V., McGovern, R. A., Kenny, C. D., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.035 · Cited by 1,107
Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor
Xu, B., Goulding, E. H., Zang, K., Cepoi, D., Cone, R. D., Jones, K. R., Tecott, L. H., & Reichardt, L. F. (2003) · Nature Neuroscience · doi:10.1038/nn1073 · Cited by 896
Di, S., Malcher‐Lopes, R., Halmos, K. C., & Tasker, J. G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-12-04850.2003 · Cited by 817
Cited by
Sorted by citations
Oyola, M. G., & Handa, R. J. (2017) · Stress · doi:10.1080/10253890.2017.1369523 · Cited by 710
“Additional evidence for CORT acting directly on PVN neurons comes from studies where targeted deletion of GR in the PVN increased CRH expression and CORT and ACTH levels in male mice (Jeanneteau et al., 2012).”
BackgroundNeural Mechanisms of Stress Resilience and Vulnerability
Franklin, T. B., Saab, B. J., & Mansuy, I. M. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.016 · Cited by 500
Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility
Gjerstad, J. K., Lightman, S. L., & Spiga, F. (2018) · Stress · doi:10.1080/10253890.2018.1470238 · Cited by 437
“As previously discussed, nuclear localization of CRTC is essential for its function and a recent study has shown that is inhibited by CORT (Jeanneteau et al., 2012).”
BackgroundThe HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain
Bellavance, M.-A., & Rivest, S. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00136 · Cited by 419
“Finally, the broad disruption of the GR allele in the CNS [GRNesCre (5)] and its targeted deletion in the forebrain [forebrain-specific GR knock-out; FBGRKO mice] (119), or the PVN all resulted in the disinhibition of the HPA axis (120).”
BackgroundGonadal steroid hormones and the hypothalamo–pituitary–adrenal axis
Handa, R. J., & Weiser, M. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.11.001 · Cited by 408
“Selective genetic disruption of GR in the PVN causes enhanced CRH immunoreactivity in the PVN and correspondingly increased levels of ACTH and corticosterone (Jeanneteau et al., 2012), which would be predicted since GR is involved in inhibitory feedback.”
Background
Metadata
- Authors
- Jeanneteau, F. D., Lambert, W. M., Ismaili, N., Bath, K. G., Lee, F. S., Garabedian, M. J., & Chao, M. V.
- Affiliations
- New York University (US)
- Department of Microbiology, New York University School of Medicine, New York, NY 10016;
- Brown University (US)
- Weill Cornell Medicine (US)
- Department of Cell Biology, Department of Physiology, Department of Neuroscience, and Department of Psychiatry, Skirball Institute of Biomolecular Medicine, and
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-01-09
- Volume
- 109
- Issue
- 4
- Pages
- 1305-1310
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3268297
- OpenAlex
- W2021067562
- Cited by
- 252
- References
- 38
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 18 · 2023: 12 · 2022: 12 · 2021: 17 · 2020: 18 · 2019: 18 · 2018: 18 · 2017: 27 · 2016: 19 · 2015: 17 · 2014: 15 · 2013: 24 · 2012: 15
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Biomedical Innovation
- National Institutes of Health (NS-21072)
- National Institute of Mental Health (R01MH086651, MH086651)
- National Institute of Allergy and Infectious Diseases (5T32 AI07180-29, T32AI007180)
- National Institute of Neurological Disorders and Stroke (R01NS021072, NS-21072, R56NS021072)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- brain-derived neurotrophic factor, glucocorticoids, corticotropin-releasing factor, hypothalamic-pituitary-adrenal axis, hypothalamus, glucocorticoid receptor, CRTC2, TrkB receptor, CREB, stress response, negative feedback
- MeSH terms
- Analysis of Variance, Animals, Corticotropin-Releasing Hormone, Glucocorticoids, Homeostasis, Hypothalamo-Hypophyseal System, Hypothalamus, Immunohistochemistry, Mice, Inbred C57BL, Neurons, Pituitary-Adrenal System, Receptors, Glucocorticoid, Transcription Factors, Trans-Activators, Mutagenesis, Site-Directed, Rats, Sprague-Dawley, Mice, Knockout, Microscopy, Confocal, Brain-Derived Neurotrophic Factor, Chromatin Immunoprecipitation, Mice, Rats, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
