Neurochemistry international最新文献

{"title":"Proteostasis and autophagy disruption by the aging-related VGVAPG hexapeptide - preliminary insights into a potential novel elastin-induced neurodegeneration pathway in an in vitro human cellular neuron model","authors":"Bartosz Skóra,&nbsp;Konrad A. Szychowski","doi":"10.1016/j.neuint.2025.105992","DOIUrl":"10.1016/j.neuint.2025.105992","url":null,"abstract":"<div><div>The hexapeptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG) is the most readily released product of elastin degradation, a process closely associated with aging. Recent studies have demonstrated the ability of this peptide to upregulate Sirtuin 2 (SIRT2) mRNA and protein expression. The correlation between HRD1 ligase (Synoviolin 1) and the degradation of SIRT2 has been previously reported in the literature. This study aimed to explore the impact of VGVAPG-induced interaction between HRD1 and SIRT2 and its effects on autophagy in differentiated SH-SY5Y cells <em>in vitro</em> (a simplified model of neurons). The results revealed that VGVAPG decreases HRD1 mRNA and protein expression while correlating with SIRT2 overexpression. Further analysis showed reduced SEL1L protein levels and an increase in p97/VCP protein expression. Additionally, enhanced phosphorylation of IRE1α indicated induction of ER stress in the tested cell model without affecting mTOR. Decreased proteasome activity and accumulation of ubiquitin were also noted. This phenomenon triggered VGVAPG-induced autophagy, as evidenced by increased expression of autophagy-related proteins ATG16L1, ATG5, ATG18, and FIP200. However, autophagy was suppressed probably as a result of VGVAPG-induced phosphorylation of ERK1/2. These findings demonstrate that the aging-related hexapeptide VGVAPG downregulates the function of the SEL1L-HRD1 complex, leading to SIRT2 accumulation and subsequent ER stress due to ERAD and UPS. This cascade, in turn, activates autophagy as an alternative clearance pathway aimed at restoring proteostasis; however, the process becomes dysregulated, leading to persistent ER stress. This dual effect may have significant implications in neurobiology, given the well-established correlation between autophagy impairment and aging-related neurodegenerative disorders.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105992"},"PeriodicalIF":4.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eslicarbazepine, a third-generation anti-seizure medication, inhibits INa but stimulates IK(M)","authors":"Te-Yu Hung ,&nbsp;Sheng-Nan Wu ,&nbsp;Chin-Wei Huang","doi":"10.1016/j.neuint.2025.105990","DOIUrl":"10.1016/j.neuint.2025.105990","url":null,"abstract":"<div><div>Eslicarbazepine (ESL) is a new antiseizure medication used to treat focal epilepsy. It is not entirely clear how ESL affects the magnitude and gating kinetics of membrane ionic currents, although a few reports have demonstrated its ability to suppress voltage-gated Na⁺ currents (<em>I</em>_Na). With the aid of patch clamp technology, docking prediction, and simulation modeling, this study was conducted to investigate the potential modifications through which ESL may induce on ionic currents, including <em>I</em>_Na, M-type K⁺ current (<em>I</em>_K(M)), and <em>erg</em>-mediated K⁺ current (<em>I</em>_K(erg)), in hippocampal neurons. ESL distinctly inhibited transient <em>I</em>_Na (<em>I</em>_Na(T)) and late <em>I</em>_Na (<em>I</em>_Na(L)), demonstrating greater potency against <em>I</em>_Na(L). ESL shifted the steady-state inactivation curve of <em>I</em>_Na(T) leftward without altering its steepness or activation curve. Additionally, ESL attenuated the tefluthrin-induced enhancement of voltage-dependent hysteresis (Hys_(V)) of persistent <em>I</em>_Na (<em>I</em>_Na(P)).</div><div>ESL increased <em>I</em>_K(M) in a concentration-dependent manner, shifting its steady-state activation curve toward more depolarized potentials and enhancing Hys(V) strength. It also increased the activity and mean open time of <em>I</em>_K(M) without affecting single-channel conductance. Minimal changes were observed in the magnitude of <em>I</em>_K(erg). Predicted docking analysis revealed that ESL binds to the hNa_V1.7 channel via hydrogen bonds and hydrophobic contacts. Simulation modeling using hippocampal CA1 pyramidal neurons demonstrated that ESL's inhibition of <em>I</em>_Na and stimulation of <em>I</em>_K(M), along with changes in their Hys(V), modulate neuronal action potential firing. Overall, these findings highlight ESL's dual effects on <em>I</em>_Na and <em>I</em>_K(M), revealing mechanisms that likely contribute to its efficacy in treatment of epilepsy.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105990"},"PeriodicalIF":4.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of cell-permeable PEP-1-Srxn1 in mitigating oxidative and ischemic damage in the hippocampus","authors":"Kyu Ri Hahn ,&nbsp;Hyun Jung Kwon ,&nbsp;Seung Myung Moon ,&nbsp;Woosuk Kim ,&nbsp;In Koo Hwang ,&nbsp;Dae Won Kim ,&nbsp;Dae Young Yoo","doi":"10.1016/j.neuint.2025.105988","DOIUrl":"10.1016/j.neuint.2025.105988","url":null,"abstract":"<div><div>In the present study, we validated the neuroprotective effects of sulfiredoxin 1 (Srxn1) against oxidative damage in HT22 cells and ischemic damage in gerbil hippocampus. To efficiently deliver Srxn1 protein into cells or the hippocampus, a PEP-1-Srxn1 fusion protein was synthesized, and efficient delivery was visualized in HT22 mouse hippocampal neuronal cells. PEP-1-Srxn1 was delivered to HT22 cells in a concentration- and incubation time-dependent manner and showed significantly higher levels at 36 h after incubation for 1 h. Morphologically, the delivered protein was localized in the cytoplasm of HT22 cells. In addition, PEP-1-Srxn1 treatment significantly ameliorated formation of reactive oxygen species, DNA fragmentation, and cell death in HT22 cells induced by treatment with 100 μM H₂O₂. In gerbils, PEP-1-Srxn1 treatment significantly alleviated transient ischemia-induced forebrain hyperactivity 1 d after ischemia and memory deficits 4 d after ischemia. Neuroprotective effects were confirmed by morphological analysis of the hippocampal CA1 region 4 or 10 d after ischemia. Treatment with PEP-1-Srxn1 significantly ameliorated the formation of reactive oxygen species and lipid peroxidation in the hippocampus during the early stages (3–12 h) of ischemia. In addition, treatment with PEP-1-Srxn1 alleviated the ischemia-induced reduction of glutathione levels in the hippocampus. PEP-1-Srxn1 also decreased ischemia-induced microglial activation and pro-inflammatory cytokine release in the hippocampus. These results suggest that PEP-1-Srxn1 is a potential therapeutic agent for reducing neuronal damage induced by oxidative or ischemic damage.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105988"},"PeriodicalIF":4.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulforaphane prevents cognitive decline and mitochondrial failure induced by hippocampal expression of caspase-3 cleaved tau","authors":"Francisca Villavicencio-Tejo ,&nbsp;Margrethe A. Olesen ,&nbsp;Estibaliz Ampuero ,&nbsp;Rodrigo A. Quintanilla","doi":"10.1016/j.neuint.2025.105991","DOIUrl":"10.1016/j.neuint.2025.105991","url":null,"abstract":"<div><div>Caspase-3 cleaved tau (truncated tau) is a pathological modification in tau protein that contributes to neurofibrillary tangle formation (NFTs) and neurodegeneration in AD. Our previous studies indicate that truncated tau affects mitochondrial health, synaptic plasticity, and cognitive performance. Therefore, we studied the effects of sulforaphane (SFN), a natural compound activator of the NRF2 antioxidant pathway present in vegetables and sprouts, on neurodegeneration and cognitive decline induced by truncated tau expression <em>in vivo</em>.</div><div>We induced a 2-month hippocampal expression of GFP, full-length (AAV-Syn-GFP-T4) and truncated tau (AAV-Syn-GFP-T4C3) using a stereotaxic injection of adeno-associated-virus-9 (AAV9) linked to GFP and a synapsin neuronal promoter in tau (−/−) mice. Hippocampal tau-expressing mice were treated with SFN, and their cognitive performance (NOR, NOL, and Barnes maze tests) and hippocampal mitochondrial function were analyzed.</div><div>Interestingly, hippocampal truncated tau expression significantly affected cognitive and memory abilities, accompanied by increased ROS and severe mitochondrial dysfunction (depolarization, ATP loss, dynamics de-regulation). Notably, the treatment with SFN (50 mg/kg/day, i.p., two weeks) prevented cognitive impairment and reduced mitochondrial bioenergetics and dynamics defects induced by hippocampal truncated tau expression.</div><div>These findings suggest a potential role of SFN in ameliorating cognitive loss and mitochondrial impairment promoted by tau pathology in neurological disorders (NDs).</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105991"},"PeriodicalIF":4.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of Fibulin-5 on early brain injury after subarachnoid hemorrhage in mice","authors":"Yume Suzuki,&nbsp;Mai Nampei,&nbsp;Fumihiro Kawakita,&nbsp;Hiroki Oinaka,&nbsp;Hideki Nakajima,&nbsp;Hidenori Suzuki","doi":"10.1016/j.neuint.2025.105989","DOIUrl":"10.1016/j.neuint.2025.105989","url":null,"abstract":"<div><div>Early brain injury (EBI) is an important cause that determines outcomes after aneurysmal subarachnoid hemorrhage (SAH). Our recent clinical study reported that a high concentration of plasma fibulin-5 (FBLN5), one of matricellular proteins, was associated with poor outcomes after SAH. The aim of this study was to investigate whether and how FBLN5 was associated with EBI during an acute phase of SAH in mice. C57BL/6 male mice underwent sham or filament perforation SAH modeling, and vehicle or four dosages (0.001, 0.01, 0.1, and 1 μg) of short or long recombinant FBLN5 (rFBLN5) were randomly administrated by an intracerebroventricular injection. Neurobehavioral test, measurements of brain water content, immunohistochemical staining, and Western blotting were performed to evaluate EBI 24 h after SAH. Short rFBLN5 had no significant effects on EBI, but administration of long rFBLN5 containing an arginine-glycine-aspartic acid motif improved neurobehavior functions depending on the dosages, without affecting brain edema. Administration of long rFBLN5 also reduced cleaved caspase-3-dependent neuronal apoptosis, associated with the inhibition of post-SAH upregulation of transforming growth factor-β1, but no significant changes in the expression level of Smad 2/3, mitogen-activated protein kinases, and another matricellular protein tenascin-C. Although further research is required to clarify the detailed mechanism, this study demonstrated for the first time that FBLN5 played a protective role against neuronal apoptosis in an acute phase of experimental SAH.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105989"},"PeriodicalIF":4.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of maternal depression and antidepressant treatment on neurotransmitters, brain regions, and mitochondrial function in rat dams","authors":"Marianna Maková ,&nbsp;Svatava Kašparová ,&nbsp;Ladislav Bačiak ,&nbsp;Daniel Gogola ,&nbsp;Zuzana Sumbalová ,&nbsp;Ingrid Brucknerová ,&nbsp;Stanislava Bukatová ,&nbsp;Michal Dubovický","doi":"10.1016/j.neuint.2025.105981","DOIUrl":"10.1016/j.neuint.2025.105981","url":null,"abstract":"<div><div>Increasing evidence suggests that mothers experience stress before or during pregnancy, which can significantly impact their GABAergic system and lead to amygdala hyperactivity. While animal models are expected to reflect the above findings in humans, the current knowledge on the effects of chronic unpredictable mild stress (CUMS) in rat dams remains insufficient. Therefore, the objective of this study was to investigate the structural and neurochemical alterations in the dorsal hippocampus, specifically gamma-aminobutyric acid (GABA) and glutamate (Glu) relative to total creatine (tCr), induced by the CUMS and the effects of antidepressant mirtazapine (MIR) treatment. Magnetic resonance imaging and proton localized magnetic resonance spectroscopy were used in rat dams at two time points to assess the reversibility of these alterations. Eight weeks post-CUMS, chronic stress induced significant alterations in hippocampal metabolism and structural changes, including lower GABA/tCr concentrations and an increased amygdala volume compared to controls. In stressed dams treated with MIR, no changes in GABA levels or amygdala volume were observed. Fourteen weeks post-CUMS, no significant changes in hippocampal neurochemistry were confirmed, while amygdala changes persisted in stressed dams. Moreover, significant time-dependent changes were observed in the amygdala and hypothalamus in the control group with MIR. Interestingly, high-resolution respirometry was performed to assess brain mitochondrial function, revealing only changes in this group. Based on these findings, we confirmed the reversibility of metabolite. Furthermore, MIR has demonstrated potential in regulating neurotransmitter levels and protecting amygdala volume after stress; however, further research is needed to fully understand its therapeutic effects.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105981"},"PeriodicalIF":4.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Supplementation with g-glutamylcysteine (γ-GC) lessens oxidative stress, brain inflammation and amyloid pathology and improves spatial memory in a murine model of AD” [Neurochem. Int. 144 (2021) 104931]","authors":"Yue Liu ,&nbsp;Zheng Chen ,&nbsp;Ben Li ,&nbsp;Hua Yao ,&nbsp;Martin Zarka ,&nbsp;Jeffrey Welch ,&nbsp;Perminder Sachdev ,&nbsp;Wallace Bridge ,&nbsp;Nady Braidy","doi":"10.1016/j.neuint.2025.105978","DOIUrl":"10.1016/j.neuint.2025.105978","url":null,"abstract":"","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105978"},"PeriodicalIF":4.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Truncation mutation of CHMP2B disrupts late endosome function but reduces TDP-43 aggregation through HSP70 upregulation","authors":"Yohei Iguchi ,&nbsp;Yuhei Takahashi ,&nbsp;Jiayi Li ,&nbsp;Yoshinobu Amakusa ,&nbsp;Yu Kawakami ,&nbsp;Takashi Yoshimura ,&nbsp;Ryo Chikuchi ,&nbsp;Madoka Iida ,&nbsp;Satoshi Yokoi ,&nbsp;Masahisa Katsuno","doi":"10.1016/j.neuint.2025.105982","DOIUrl":"10.1016/j.neuint.2025.105982","url":null,"abstract":"<div><div>TAR DNA-binding protein 43 (TDP-43)-positive cytoplasmic aggregation is a pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). This aggregation contributes substantially to the neurodegeneration of ALS and FTLD. The endosome, a key component of membrane trafficking in eukaryotic cells and is involved in the autophagy–lysosome pathway. Endosome-related genes such as <em>CHMP2B</em>, <em>Alsin</em>, and <em>TMEM106B,</em> are either causative or act as genetic modifiers in ALS and FTLD. However, the association between endosomal functions and TDP-43 aggregations remain poorly understood. The C-terminal truncation mutation <em>CHMP2B</em>, which causes frontotemporal dementia associated with chromosome 3 (FTD3), disrupts late endosome (LE)–lysosomes fusion. Nevertheless, FTD3 does not induce TDP-43 pathology. In this study, we showed that <em>CHMP2B</em> mutation-induced LE dysfunction promotes TDP-43 aggregate degradation through enhanced recruitment to juxtanuclear quality control compartments. Transcriptomic analysis revealed that <em>CHMP2B</em>^{<em>intron5</em>} overexpression upregulates HSP70 expression. New insights into the connection between <em>CMHP2B</em> and HSP70 as well as the role of HSP70-mediated membrane trafficking in TDP-43 aggregation, offer a valuable understanding of the disease mechanism of ALS and FTLD.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105982"},"PeriodicalIF":4.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA sequencing analysis identifies sex differences in transcriptional signatures in the dorsal striatum of female and male rats after withdrawal from methamphetamine self-administration","authors":"Vaibhav V. Gujar ,&nbsp;Atul P. Daiwile ,&nbsp;Vikrant Palande ,&nbsp;Jean Lud Cadet","doi":"10.1016/j.neuint.2025.105980","DOIUrl":"10.1016/j.neuint.2025.105980","url":null,"abstract":"<div><div>Significant methamphetamine (METH)-induced behavioral differences exist between the two sexes of humans and other animals. These dissimilarities may be related to sexual dimorphism in baseline molecular and biochemical mechanisms in brain reward neuroanatomical pathways. As a first step towards identifying sex-based differences in methamphetamine-induced transcriptional signatures, we used RNA sequencing analysis to measure genome-wide changes in gene expression in the dorsal striatum of rats that had self-administered METH. We trained rats to self-administer METH (0.1 mg/kg/infusion, i.v.) using two 3-hr daily sessions (with 30 min time out between sessions) for 20 days. Control rats self-administered saline under similar conditions. This was followed by drug seeking tests on withdrawal days 3 (WD3) and 30 (WD30). Behavioral results show that male rats took more METH than female rats. In both male and female rats, some animals escalated (high-takers) whereas others did not escalate (low-takers) their METH intake during the behavioral experiment. Rats were euthanized 24 h after the second drug seeking test. RNA was extracted from the dorsal striatum (dSTR) and used in RNA sequencing analysis. The data identified substantial baseline differences in gene expression between female and male control rats. In addition, METH use and withdrawal were associated with significant sex-related differences in changes in striatal gene expression, with minimal overlaps of altered mRNAs. Thus, the present results provide further supporting evidence for sexually dimorphic responses to METH exposure. These observations support the notion of sex-specific approaches to the treatment of patients who suffer from METH use disorder.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"187 ","pages":"Article 105980"},"PeriodicalIF":4.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-canonical STAT3 pathway induces alterations of mitochondrial dynamic proteins in the hippocampus of an LPS-induced murine neuroinflammation model","authors":"Périne Millot ,&nbsp;Laurine Duquesne ,&nbsp;Carine San ,&nbsp;Baptiste Porte ,&nbsp;Claire Pujol ,&nbsp;Benoit Hosten ,&nbsp;Jacques Hugon ,&nbsp;Claire Paquet ,&nbsp;François Mouton-Liger","doi":"10.1016/j.neuint.2025.105979","DOIUrl":"10.1016/j.neuint.2025.105979","url":null,"abstract":"<div><div>The activation of STAT3 is a crossroads of cellular regulation, induced in its canonical pathway by phosphorylation on a critical tyrosine residue (Y705). The existence of a STAT3 non-canonical signaling mechanisms, induced by phosphorylation at serine 727 (S727), has been recently identified in vitro. After cytoplasmic activation, non-canonical STAT3 could move to the level of mitochondria-endoplasmic reticulum contacts (MERCs).</div><div>We have previously shown that LPS injections in mouse model induce STAT3 canonical pathway, leading to its nuclear translocation and to neuroinflammation. However, the effects of LPS on activation of the non-canonical pathway and its consequences on protein complexes of MERCs remain to be determined. In an <em>in vivo</em> LPS mouse model, we found that systemic inflammation induces in hippocampus the non-canonical STAT3 pathway. LPS-induced STAT3 affects specifically MERC protein BAP31, and that of a mitochondrial membrane protein known to interact with it, TOM40. These findings shed light on the role of STAT3 on mitochondrial – endoplasmic reticulum interaction under inflammatory conditions, offering new perspectives for targeting mitochondrial function and STAT3 activation in disease contexts.</div></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":"186 ","pages":"Article 105979"},"PeriodicalIF":4.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143815987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}