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Cited by 8Mitochondrial Function and PathologyNeuroinflammation and Neurodegeneration MechanismsAutophagy in Disease and Therapy

Transcript and Lipid Profile Alterations in Astrocyte‐Neuron Mitochondrial Transfer Under Lipopolysaccharide Exposure: An In Vitro Study

Open access
Kan, Yufei, Wang, Hong, Lin, Huaying, Li, Yongfa, Pei, Shuaijie, Cui, Yan, Xie, Keliang, Chen, Hongguang +1 more·2025·Journal of Neurochemistry
DOI 10.1111/jnc.70003PMC PMC11791887
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Abstract

Sepsis‐associated encephalopathy (SAE) is a brain dysfunction for which no effective therapy currently exists. Recent studies suggest that transferring mitochondria from astrocytes to neurons may benefit SAE patients, though the underlying mechanism remains unclear. We cultured astrocytes and neurons from mice in vitro. Astrocytes were stimulated with lipopolysaccharide (LPS) for 24 h, and the astrocyte‐conditioned medium (ACM) was collected. Neuronal cultures were then treated with ACM or mitochondria‐depleted ACM (mdACM) for further analysis. Mitochondrial transfer was examined under a fluorescence microscope. Western blotting analyzed the protein expression of genes related to apoptosis and mitochondrial metabolism. RNA sequencing and mass spectrometry were employed to investigate the mechanisms underlying mitochondrial transfer. Astrocyte‐derived mitochondria migrated toward and connected with LPS‐exposed neurons. The addition of ACM significantly attenuated LPS‐induced alterations in the proteins linked to apoptosis and mitochondrial dynamics. RNA sequencing revealed notable alterations in the transcript profile of neurons upon ACM treatment, highlighting the involvement of mitochondria metabolism, inflammation, and apoptosis‐related factors. Additionally, mitochondrial transfer modified the lipid composition of neurons, increasing phosphatidylserine levels, which correlated with neuroinflammation and enriched pathways related to cytokine and MAPK signaling. Our findings suggest that astrocyte‐neuron mitochondrial transfer holds therapeutic potential for alleviating SAE, possibly through the anti‐inflammatory effects of lipids, particularly phosphatidylserine. image

AI snapshot

Written from the paper’s full text.

TL;DR

In an in vitro mouse astrocyte–neuron model, astrocyte-derived mitochondria transferred to LPS-exposed neurons and ACM treatment attenuated LPS-induced neuronal injury, apoptosis, and mitochondrial-dynamics protein changes. RNA-seq and lipidomics linked mitochondrial transfer to transcriptomic shifts and increased neuronal phosphatidylserine, especially PS species correlated with neuroinflammation pathways.

Key findings

  • Astrocyte-derived mitochondria migrated toward and reconnected with LPS-exposed neurons; ACM, but not mitochondria-depleted ACM (mdACM), reversed LPS-induced changes in neuronal viability, TNF-α, membrane potential, Bax, cleaved caspase-3, Bcl-2, Pgc-1α, Mfn2, and Drp1 (all p < 0.05 in reported comparisons).
  • RNA-seq identified 3427 DEGs between LPS + ACM and LPS + mdACM neurons: 2184 downregulated and 1243 upregulated. Enrichment implicated mitochondrial metabolism, inflammation, apoptosis, phosphorylation, phospholipid binding, and phosphatidylserine binding.
  • Lipidomics showed increased neuronal phosphatidylserine (PS) after mitochondrial transfer: 6.725% vs. 3.624%. Among top 20 differential lipid species, 18 PS species decreased in the listed table, and PS with chain length C36–C40 was higher in LPS + ACM, most pronounced at C36.
  • KEGG analysis linked DEGs to inflammation-related pathways including cytokine–cytokine receptor interaction, Toll-like receptor signaling, and MAPK signaling; DEGs correlated most strongly with PS (18:0/22:5)-H and PS (18:0/18:1)-H.

Methods

  • Primary mouse cortical neurons and astrocytes were cultured in vitro. Astrocytes were stimulated with 1 μg/mL LPS for 24 h to generate astrocyte-conditioned medium (ACM); mdACM was produced by 0.2-μm filtration. Neurons were treated for 24 h with PBS, LPS, LPS + ACM, or LPS + mdACM.
  • Mitochondrial transfer was assessed with mito-RFP–labeled astrocytes and mito-GFP–labeled neurons using high-content imaging. Neuronal viability, ATP, membrane potential, TNF-α, and apoptosis/mitochondrial proteins were measured by CCK-8, colorimetric kits, ELISA, and Western blotting.
  • RNA-seq identified DEGs with |log2FC| > 1 and adjusted p < 0.05, followed by GO and KEGG enrichment. LC–MS/MS lipidomics used OPLS-DA with VIP > 1 and p < 0.05 to identify differential lipids, followed by Pearson correlation between DEGs and lipids. Statistical comparisons used one-way ANOVA or unpaired t-tests, with p < 0.05 considered significant.

Limitations

  • The paper states that the ex vivo culture system may not fully replicate the in vivo environment, limiting translational impact, and that further studies are needed to elucidate precise molecular mechanisms and validate findings with additional functional assays and in vivo studies.
  • The text also makes evident small sample sizes (e.g., n = 3 for Western/RNA-seq, n = 4 for extracellular mitochondria assays, n = 6 for lipidomics), sample size determined by logistical and financial constraints rather than formal power analysis, no formal outlier test, and no multiple-comparison correction for metabolomics.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/jnc.70003

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

8 of 18 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Our results are consistent with previous studies showing promise for Drp1 inhibitor Mdivi-1, cyclophilin D, and mitochondria-targeting peptide SS-31 in treating SAE.

    “Our results are consistent with previous studies showing promise for agents like Drp1 inhibitor Mdivi‐1 (Deng et al. 2018), mitochondrial isomerase cyclophilin D (CypD) (Kobayashi et al. 2022), and mitochondria‐targeting peptide SS‐31 (Wu et al. 2015) in treating SAE.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Deng et al. 2018 source
    • cites Kobayashi et al. 2022 source

      The Discussion (page unavailable) reports improved survival and reduced brain damage in septic CypD-knockout mice, supporting CypD as a potential therapeutic target for SAE. It did not test CypD as an administered agent or establish a treatment for SAE; the authors also say the direct causal relationship with improved outcomes is not yet clear. The other two agents have separate citations and are not assessed here. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Wu et al. 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Findingown data

    RNA sequencing revealed notable alterations in the transcript profile of neurons upon ACM treatment, highlighting the involvement of mitochondria metabolism, inflammation, and apoptosis-related factors.

    “RNA sequencing revealed notable alterations in the transcript profile of neurons upon ACM treatment, highlighting the involvement of mitochondria metabolism, inflammation, and apoptosis‐related factors.”
    Quote in the paperSubstantial claim
  • Findingown data

    Astrocyte-derived mitochondria migrated toward and connected with LPS-exposed neurons.

    “Astrocyte‐derived mitochondria migrated toward and connected with LPS‐exposed neurons.”
    • Also stated in: § Mitochondrial Transfer From Astrocytes to Neurons Mitigates LPS‐Induced Neuronal Disruptions · plain
      “After introducing ACM to the neurons, astrocyte‐tagged mitochondria began migrating toward the neurons within an hour and started reconnecting after 3 h (Figure 1C).”
    Quote in the paperSubstantial claim
  • Findingown data

    ACM, but not mdACM, reversed LPS-induced alterations in neuronal viability.

    “ACM, but not mdACM, recovered neuronal viability after sepsis.”
    • Also stated in: § Mitochondrial Transfer From Astrocytes to Neurons Mitigates LPS‐Induced Neuronal Disruptions · plain
      “ACM reversed the alterations in neuronal viability (Figure 2A), TNF‐α levels (Figure 2B), and membrane potential (Figure 2C) induced by LPS.”
    Quote in the paperSubstantial claim
  • Findingown data

    The addition of ACM significantly attenuated LPS-induced alterations in the proteins linked to apoptosis and mitochondrial dynamics.

    “The addition of ACM significantly attenuated LPS‐induced alterations in the proteins linked to apoptosis and mitochondrial dynamics.”
    Quote in the paperSubstantial claim
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Premisecitation

    PS (18:0/22:5)-H and PS (18:0/18:1)-H have known anti-inflammatory properties.

    “which have known anti‐inflammatory properties.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites Listenberger et al. 2003 source

      The Results passages describe fatty-acid species in triglycerides, and the Discussion describes protection against fatty-acid-induced lipotoxicity. Searches for phosphatidylserine, the named PS species, and anti-inflammatory effects found no passage addressing whether those PS species have anti-inflammatory properties. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
    • cites Medina and Tabernero 2002 source
    • cites Choi et al. 2022 source

      The Introduction and Results section 3.2 discuss the anti-inflammatory effects of DoPE, a docosapentaenoic-acid derivative, in PM10-stimulated keratinocytes. Searches for PS (18:0/22:5)-H, PS (18:0/18:1)-H, and phosphatidylserine found no passage addressing the anti-inflammatory properties of either claimed compound. Page numbers were not available in our copy. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Oleic acid, a component of PS (18:0/18:1)-H, mitigates lipotoxicity and promotes neuronal differentiation.

    “Oleic acid, a component of PS (18:0/18:1)‐H, mitigates lipotoxicity and promotes neuronal differentiation (Listenberger et al. 2003; Medina and Tabernero 2002).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Listenberger et al. 2003 source

      The Results section reports that oleate prevented palmitate-induced apoptosis in cultured CHO cells, supporting the lipotoxicity portion of the claim. The paper does not address neuronal differentiation or identify oleic acid as a component of PS (18:0/18:1)-H. The Discussion also notes that oleate can be toxic when triglyceride synthesis is impaired. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Medina and Tabernero 2002 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Sample size was determined based on previous studies with similar designs due to logistical and financial constraints.

    “Due to logistical and financial constraints, our sample size was determined based on previous studies with similar designs (Hayakawa et al. 2016; Juraszek and Nalecz 2016).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hayakawa et al. 2016 source
    • cites Juraszek and Nalecz 2016

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Docosapentaenoic acid (DPA), a key component of PS (18:0/22:5)-H, demonstrates potent anti-inflammatory effects, enhancing macrophage polarization and reducing ROS production.

    “Docosapentaenoic acid (DPA), a key component of PS (18:0/22:5)‐H, demonstrates potent anti‐inflammatory effects, enhancing macrophage polarization and reducing ROS production (Choi et al. 2022; Ma et al. 2020).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Choi et al. 2022 source

      The Introduction identifies DoPE as a DPA-derived compound, and the Conclusion reports that DoPE reduced ROS production and modulated IL-6 in PM10-stimulated HaCaT keratinocytes. The paper does not establish those effects for DPA itself, identify DPA as a component of PS (18:0/22:5)-H, or report enhanced macrophage polarization. The full-text copy supplies no page numbers for these sections. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Ma et al. 2020

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Previous studies have highlighted the neuroprotective roles of IL-36 and IL-27, and the inflammatory effects of IL-20RB and IL-11.

    “Previous studies have highlighted the neuroprotective roles of IL‐36 and IL‐27, and the inflammatory effects of IL‐20RB and IL‐11 (Dayton et al. 2021; Ng et al. 2020; Apetoh et al. 2010; Chen et al. 2022; Me et al. 2021).”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Dayton et al. 2021 source
    • cites Ng et al. 2020

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Apetoh et al. 2010 source

      The Results section (‘AhR controls the IL-27-mediated inhibition of EAE’) reports that IL-27 treatment of donor T cells reduced the incidence of experimental autoimmune encephalomyelitis, supporting a protective role in this CNS autoimmune disease model. Our copy does not address IL-36, IL-20RB, or IL-11, or establish neuroprotection beyond that model. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Mitochondrial transfer modified the lipid composition of neurons, increasing phosphatidylserine levels, which correlated with neuroinflammation and enriched pathways related to cytokine and MAPK signaling.

    “Additionally, mitochondrial transfer modified the lipid composition of neurons, increasing phosphatidylserine levels, which correlated with neuroinflammation and enriched pathways related to cytokine and MAPK signaling.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Astrocyte-tagged mitochondria began migrating toward the neurons within an hour and started reconnecting after 3 h.

    “After introducing ACM to the neurons, astrocyte‐tagged mitochondria began migrating toward the neurons within an hour and started reconnecting after 3 h (Figure 1C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When conditioned media from astrocytes were filtered via 0.2-μm filters, the number of activated mitochondria and the ATP levels were decreased.

    “When conditioned media from astrocytes were filtered via 0.2‐μm filters, the number of activated mitochondria and the ATP levels were decreased (Figure 1A,B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Phosphorylation process involves genes such as synaptotagmins family (Syt7, Syt8, Sytl1, and Sytl2) and annexins (Anxa3, Anxa7, Anxa2, and Anxa1), which are linked to inflammatory pathway, implicating these genes as potential therapeutic targets in SAE.

    “Phosphorylation process involves genes such as synaptotagmins family (Syt7, Syt8, Sytl1, and Sytl2) and annexins (Anxa3, Anxa7, Anxa2, and Anxa1), which are linked to inflammatory pathway, further implicating these genes as potential therapeutic targets in SAE.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    RNA-seq identified 3427 DEGs, with 2184 being downregulated and 1243 upregulated.

    “RNA‐seq identified 3427 DEGs, with 2184 being downregulated and 1243 upregulated (Figure 3C; Data S2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Biological analysis revealed significant genetic variations between ACM and mdACM groups, with GO annotation showing DEGs primarily associated with phospholipid binding.

    “Biological analysis revealed significant genetic variations between ACM and mdACM groups, with GO annotation showing DEGs primarily associated with “phospholipid binding.””
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The addition of ACM to the LPS group amplified the expression of Pgc-1α while reversing the LPS-induced changes in the expression of Mfn2 and Drp1.

    “The addition of ACM to the LPS group amplified the expression of Pgc‐1α while reversing the LPS‐induced changes in the expression of Mfn2 and Drp1 (Figure 2H–K).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The LPS group showed increased expression of Pgc-1α, decreased expression of Mfn2, and increased expression of Drp1 compared to the PBS group (p < 0.05).

    “Correspondingly, the LPS group showed increased expression of the Pgc‐1α, a protein related to mitochondrial biosynthesis, decreased expression of Mfn2, a mitochondrial fusion protein, and increased expression of Drp1, a protein related to mitochondrial dynamics (p < 0.05) compared to the PBS group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Transcriptomic and lipidomic analyses revealed changes in gene expression and lipid profiles associated with neuroinflammation, with a significant correlation between DEGs and PS.

    “Transcriptomic and lipidomic analyses revealed changes in gene expression and lipid profiles associated with neuroinflammation, with a significant correlation between DEGs and PS.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Table 1 presents the top 20 genes with the highest fold-changes, most of which were significantly downregulated.

    “Table 1 presents the top 20 genes with the highest fold‐changes, most of which were significantly downregulated.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Our findings revealed significant enrichment in the Toll-like receptor signaling pathway, with lipid analysis linking PS (18:0/22:5)-H to inflammation-related pathways.

    “Our findings also revealed significant enrichment in the Toll‐like receptor signaling pathway, with lipid analysis linking PS (18:0/22:5)‐H to inflammation‐related pathways.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LPS exposure increased the expression of BAX and cleaved caspase-3 while decreasing Bcl-2 in neurons compared to the PBS group (p < 0.05).

    “LPS exposure increased the expression of BAX and cleaved caspase‐3 while decreasing Bcl‐2 in neurons compared to the PBS group (p < 0.05).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Astrocyte-neuron mitochondrial transfer holds therapeutic potential for alleviating SAE, possibly through the anti-inflammatory effects of lipids, particularly phosphatidylserine.

    “Our findings suggest that astrocyte‐neuron mitochondrial transfer holds therapeutic potential for alleviating SAE, possibly through the anti‐inflammatory effects of lipids, particularly phosphatidylserine.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro LPS-stimulated astrocyte-neuron co-culture model reflects the pathophysiology of SAE in vivo.
    • Rests on an assumption: Phosphatidylserine has anti-inflammatory effects.

  • May combine two claims.

    Interpretationcitation

    These findings highlight the neuroprotective effects of fatty acids like oleic acid and DPA, suggesting their potential in treating SAE.

    “These findings highlight the neuroprotective effects of fatty acids like oleic acid and DPA, suggesting their potential in treating SAE.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The therapeutic effect may be attributed to anti-inflammatory functions of lipids, especially PS, which may change mitochondrial membrane composition and preserve mitochondrial protein integrity.

    “This phenomenon could be attributed to the anti‐inflammatory functions of lipids, especially PS, which may change the composition of mitochondrial membranes and preserve the integrity of mitochondrial proteins.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Polydatin and citrate caffeine have demonstrated neuroprotective effects by improving mitochondrial function and reducing inflammation, underscoring the importance of mitochondrial health in SAE therapy.

    “Additionally, Polydatin derived from Polygonum cuspidatum (Gao et al. 2015) and citrate caffeine (Hu et al. 2022) have demonstrated neuroprotective effects by improving mitochondrial function and reducing inflammation, underscoring the importance of mitochondrial health in SAE therapy.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Gao et al. 2015 source
    • cites Hu et al. 2022

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    No formal statistical test for outliers was conducted in this study.

    “No formal statistical test for outliers was conducted in this study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Oleic acid and DPA provide neuroprotection by lowering inflammation, stimulating macrophage polarization through MAPK signaling, and triggering neuronal neogenesis.

    “Oleic acid and DPA provide neuroprotection by lowering inflammation, stimulating macrophage polarization through MAPK signaling, and triggering neuronal neogenesis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Astrocyte-mediated mitochondrial transfer is a potential therapeutic strategy for SAE, and PS may mitigate neuronal damage.

    “These findings emphasize the potential of astrocyte‐mediated mitochondrial transfer as a therapeutic strategy for SAE and underscore the role of PS in mitigating neuronal damage.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The identified DEGs are associated with critical biological processes, including phosphorylation, mitochondrial translocation, and phospholipid binding, highlighting their potential roles in ATP production, cellular damage mitigation, and neuroinflammation.

    “these data suggest that the identified DEGs are associated with critical biological processes, including phosphorylation, mitochondrial translocation, and phospholipid binding, this highlights their potential roles in ATP production, cellular damage mitigation, and neuroinflammation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Mitochondria play a central role in cellular energy generation and can impact oxidative phosphorylation.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All experimental procedures were conducted in accordance with the 'Guide for the care and use of laboratory animals' (8th Edition, USA).

    “All experimental procedures were conducted in accordance with the ‘Guide for the care and use of laboratory animals’ (8th Edition, USA).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    ACM exposure induces significant transcriptome changes in LPS-treated neurons, potentially influencing mitochondrial metabolism, inflammation, and apoptosis.

    “These findings suggest that ACM exposure induces significant transcriptome changes in LPS‐treated neurons, potentially influencing the mitochondrial metabolism, inflammation, and apoptosis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    For metabolomics, no multiple comparison correction was applied due to the limited number of comparisons.

    “For metabolomics, no multiple comparison correction was applied due to the limited number of comparisons.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The ethics approval reference number is IRB2023-DW-18.

    “The ethics approval reference number is IRB2023‐DW‐18.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Mitochondrial transfer alters the lipid composition of neurons, impacting membrane characteristics and resulting in an increase in PS content.

    “These findings suggested that mitochondrial transfer alters the lipid composition of neurons, impacting membrane characteristics and resulting in an increase in PS content.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Changes in the chain length of phospholipid subclasses directly affect membrane fluidity.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    No data points were excluded based on outlier detection.

    “No data points were excluded based on outlier detection.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Phosphorylation is a crucial process related to ATP production.

    “a crucial process related to Adenosine triphosphate (ATP) production (Wilson 2017)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wilson 2017 source

  • May combine two claims.

    Interpretationown data

    Mitochondrial transfer between astrocytes and neurons mitigated LPS-induced apoptosis and altered mitochondrial metabolism.

    “Mitochondrial transfer between astrocytes and neurons, mitigated LPS‐induced apoptosis and altered mitochondrial metabolism.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

    Study design and conductnone given

    The ex vivo culture system may not fully replicate the in vivo environment, limiting the translational impact.

    “The ex vivo culture system may not fully replicate the in vivo environment, limiting the translational impact.”
    Quote in the paperNot a substantial claim
34 of 34

  • The paper relies on this without support.

    The 0.2-μm filter depletes mitochondria from ACM without removing other bioactive factors that could affect neurons.

    “The mdACM was obtained by filtering out the mitochondria from the ACM using a 0.2‐μm filter.”
    “When conditioned media from astrocytes were filtered via 0.2‐μm filters, the number of activated mitochondria and the ATP levels were decreased (Figure 1A,B).”

  • The paper relies on this without support.

    The in vitro LPS-stimulated astrocyte-neuron co-culture model reflects the pathophysiology of SAE in vivo.

    “we stimulated mouse astrocytes with lipopolysaccharide (LPS), a well‐established method to induce inflammation in SAE studies (Chen et al. 2020; Zhuang et al. 2020), and cultured mouse neurons in astrocyte‐conditioned medium (ACM) or mitochondria‐depleted ACM (mdACM) in the presence of LPS.”

  • The paper relies on this without support.

    Phosphatidylserine has anti-inflammatory effects.

    “Our findings suggest that astrocyte‐neuron mitochondrial transfer holds therapeutic potential for alleviating SAE, possibly through the anti‐inflammatory effects of lipids, particularly phosphatidylserine.”

  • The paper relies on this without support.

    Mitochondria play a central role in cellular energy generation and can impact oxidative phosphorylation.

    “Given that mitochondria play a central role in cellular energy generation and can impact oxidative phosphorylation”

  • The paper relies on this without support.

    Changes in the chain length of phospholipid subclasses directly affect membrane fluidity.

    “Changes in the chain length of phospholipid subclasses directly affect membrane fluidity.”

  • The paper relies on this without support.

    TAM receptors are involved in phagocyte-mediated control.

    “TAM receptors, which are involved in phagocyte‐mediated control”

  • The paper relies on this without support.

    Mg53 prevents LPS-induced mitochondrial dysfunction and apoptosis.

    “Mg53, a gene known for preventing LPS‐induced mitochondrial dysfunction and apoptosis”
7 of 7

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Consistentt(6) = 3.057reported p = .0223 · recomputed p = .022

    “t (6) = 3.057, p = .0223”

  • Consistentt(6) = 7.778reported p = .0002 · recomputed p < .001

    “t (6) = 7.778, p = .0002”

  • ConsistentF(3, 28) = 51.15reported p < .0001 · recomputed p < .001

    “F (3,28) = 51.15, p < .0001”

  • ConsistentF(3, 12) = 172.7reported p < .0001 · recomputed p < .001

    “F (3,12) = 172.7, p < .0001”

  • ConsistentF(3, 12) = 52.39reported p < .0001 · recomputed p < .001

    “F (3,12) = 52.39, p < .0001”

  • ConsistentF(3, 8) = 20.15reported p = .0004 · recomputed p < .001

    “F (3,8) = 20.15, p = .0004”

  • ConsistentF(3, 8) = 18.65reported p = .0006 · recomputed p < .001

    “F (3,8) = 18.65, p = .0006”

  • ConsistentF(3, 8) = 16.5reported p = .0009 · recomputed p < .001

    “F (3,8) = 16.50, p = .0009”

  • ConsistentF(3, 8) = 24.01reported p = .0002 · recomputed p < .001

    “F (3,8) = 24.01, p = .0002”

  • ConsistentF(3, 8) = 14.44reported p = .0014 · recomputed p = .001

    “F (3,8) = 14.44, p = .0014”

  • ConsistentF(3, 8) = 18.53reported p = .0006 · recomputed p < .001

    “F (3,8) = 18.53, p = .0006”

11 of 11

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

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Authors
Kan, Y., Wang, H., Lin, H., Li, Y., Pei, S., Cui, Y., Xie, K., Chen, H., & Yu, Y.
Affiliations
  • Tianjin Medical University General Hospital (CN)
  • Department of Anesthesiology Shanxi Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences Taiyuan Shanxi Province PR China
  • Chongqing University (CN)
  • Tianjin Medical University (CN)
Corresponding author
  • Xie, Keliang
  • Chen, Hongguang
  • Yu, Yonghao
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2025-02
Volume
169
Issue
2
Pages
e70003-e70003
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/jnc.70003
PMC
PMC11791887
OpenAlex
W4407141881
Cited by
8
References
46
Citations by year
2026: 4 · 2025: 4
FWCI
2.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neurochemistry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (IEC/NSFC/223509)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
sepsis-associated encephalopathy, lipopolysaccharide, astrocyte-conditioned medium, mitochondrial metabolism, apoptosis, mitochondrial dynamics, phosphatidylserine, lipid profile, neuroinflammation, MAPK signaling, transcriptome
MeSH terms
Animals, Astrocytes, Cells, Cultured, Lipopolysaccharides, Mice, Inbred C57BL, Mitochondria, Neurons, Lipid Metabolism, Mice

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-02.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-02.

Cited sources are checked by gpt-6-sol.

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 ›

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