Journal of Neurochemistry最新文献

{"title":"Neuroinflammation and Graft Survival in Pluripotent Stem Cell-Derived Therapies for the Central Nervous System.","authors":"Lucía Sánchez, Candela Magalí Rodriguez, Fernando J Pitossi","doi":"10.1111/jnc.70540","DOIUrl":"10.1111/jnc.70540","url":null,"abstract":"<p><p>Recently, Japan conditionally approved the first cell transplantation therapy for a central nervous system disorder using induced pluripotent stem cells as the source of dopaminergic progenitors to treat Parkinson's disease. This milestone was achieved almost 40 years after the first cell therapy trial for Parkinson's disease in Lund, Sweden, and 18 years after the first clinical trial using oligodendrocyte progenitors derived from pluripotent stem cells for spinal cord injury. In this review, we update the current state of development of cell therapies based on pluripotent stem cells for diseases of the central nervous system and discuss the potential effects of neuroinflammation on these cell therapies. Focusing on Parkinson's disease, we summarize data showing the functional relevance of tumor necrosis factor-alpha for the differentiation and viability of pluripotent stem cell-derived dopaminergic progenitors and its dual effects on endogenous dopaminergic neurons, as presented at the Second Meeting of the Latin American Glia Club, held April 7-9, 2025, in Buenos Aires, Argentina. In addition, we propose areas of cell transplantation in Parkinson's disease in which research efforts could be focused and present a cautionary note on the use of non-selective anti-tumor necrosis factor-α therapies alongside pluripotent stem cell-derived dopaminergic progenitor transplantation. Finally, we provide an in-depth list of TNF receptor agonists and antagonists and specific TNF-mediated cell-death inhibitors and discuss their properties as possible candidates for increasing dopaminergic progenitor survival after transplantation in patients with Parkinson's disease.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 9","pages":"e70540"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of a Common Marmoset Lineage Carrying a Frameshift Mutation in SETD1A, a Schizophrenia Risk Gene.","authors":"Zefeng Wei, Harumi Nakao, Yuichi Hiraoka, Maria Harbers, Yukiko Abe, Motoki Goto, Moe Tamano, Mai Saeki, Yusuke Kishi, Atsu Aiba","doi":"10.1111/jnc.70546","DOIUrl":"10.1111/jnc.70546","url":null,"abstract":"<p><p>Appropriate histone modifications are essential for maintaining functional chromatin structure and gene expression, and dysfunction of their regulators has been linked to a variety of diseases. Among these modifications, trimethylation of lysine 4 on histone H3 (H3K4me3) is a well-characterized epigenetic mark enriched at transcription start sites of actively transcribed genes. H3K4me3 regulates gene transcription by recruiting transcription factors, facilitating chromatin accessibility, and preventing DNA methylation. In mammals, methylation of H3K4 is catalyzed by a family of histone methyltransferases including SET domain containing 1A (SETD1A), which is primarily responsible for genome-wide deposition of H3K4me2/3. Loss-of-function variants in SETD1A, highlighting its critical role in brain development and cognitive function, are strongly associated with schizophrenia (SCZ) and other neurodevelopmental disorders, but the underlying mechanisms remain largely unclear. To better understand the epigenetic and neurobiological consequences of SETD1A dysfunction, non-human primate models can serve as a useful tool because of their close evolutionary relationship to humans and highly developed cognitive abilities. In this study, we established a genetically engineered common marmoset (Callithrix jacchus) lineage carrying a frameshift mutation in SETD1A, which is, to the best of our knowledge, the first non-human primate lineage carrying a mutation in an epigenetic regulatory gene associated with SCZ, and confirmed germline transmission of the mutant allele. In a comparison between fibroblasts derived from one SETD1A mutant and one wild-type marmoset, the mutant showed a lower SETD1A protein level, modest differences in H3K4me3 deposition, and broader differences in gene expression profiles. Although these molecular observations require validation using additional biological replicates, the establishment of this SETD1A mutant marmoset lineage provides a valuable platform for bridging molecular mechanisms with primate neurobiology and for investigating the role of epigenetic regulation in the pathophysiology of neuropsychiatric and neurodevelopmental disorders.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 9","pages":"e70546"},"PeriodicalIF":4.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Proteinopathy to Immunopathy in Alzheimer's Disease—A Role for Astrocytic Calcineurin?","authors":"Dmitry Lim,&nbsp;Laura Tapella","doi":"10.1111/jnc.70543","DOIUrl":"https://doi.org/10.1111/jnc.70543","url":null,"abstract":"&lt;p&gt;The contemporary version of the most widely accepted model of Alzheimer's disease (AD), the β-amyloid cascade hypothesis, identifies β-amyloid oligomers as the primary neurotoxic species. Arising either from genetic mutations or environmental and lifestyle predisposing factors (collectively termed the exposome), β-amyloid oligomers gradually disrupt homeostatic cellular processes. At the cellular level, these alterations largely converge on two central pathobiological domains: proteinopathy (the disruption of cellular protein homeostasis) and immunopathy (the activation of immune-inflammatory pathways). Alterations of protein homeostasis and immune-inflammatory reactions evolve concomitantly in a self-amplifying vicious cycle that shapes the spatio-temporal progression of AD. A mechanistic understanding of this proteinopathy–immunopathy crosstalk is fundamental to identifying preventive and disease-modifying therapies. Here, we propose that the calcium/calmodulin-activated phosphatase calcineurin, expressed in astroglial cells, serves as a pivotal molecular switch between protein homeostasis and neuroinflammation, representing a potential target for therapeutic intervention.&lt;/p&gt;&lt;p&gt;Protein homeostasis encompasses a tightly regulated sequence of events ranging from ribosomal translation to post-translational maturation, trafficking, secretion, and degradation. Robust and conserved quality-control mechanisms, such as endoplasmic reticulum (ER)-associated degradation and the unfolded protein response (UPR), protect the proteostatic machinery during stress. Accordingly, the concept of “proteinopathy” should not be restricted to the classical accumulation of canonical misfolded proteins (e.g., β-amyloid, tau, α-synuclein), but should incorporate all stages of cellular proteostasis. Within this broader framework, the intracellular accumulation of misfolded β-amyloid represents merely one of several potential primary triggers of impaired protein turnover. In addition to β-amyloid, diverse damage- and pathogen-associated molecular patterns (DAMPs and PAMPs) released during comorbid conditions, such as metabolic dysfunction (Type 2 diabetes, obesity), infections, trauma, ischemia, toxins, and psychiatric co-morbidities, can function as primary drivers of cellular stress and proteostatic disruption.&lt;/p&gt;&lt;p&gt;These distinct primary insults affect individual components of the proteostatic network differently, resulting in a spectrum of alterations that evolve dynamically and asynchronously throughout the preclinical and clinical stages of AD (De Strooper and Karran &lt;span&gt;2016&lt;/span&gt;). These disruptions include impaired ribosomal protein synthesis, asynchronous activation of ER stress/UPR pathways, defective autophagic flux and lysosomal degradation, reduced proteasomal activity, and upregulation of the inflammasome—the latter directly linking dysproteostasis to neuroinflammation. This asynchronous evolution of protein dyshomeostasis culminates in full UPR act","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70543","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AHA1 Regulates Aβ Production via Modulation of APP Abundance and γ-Secretase Assembly","authors":"Arshad Ali Noorani,&nbsp;Sadequl Islam,&nbsp;Emma Filip,&nbsp;Kevin Catalfano,&nbsp;Shravan Paswan,&nbsp;Vaishnavi Nagarajan,&nbsp;Heather M. Wilkins,&nbsp;Brian S. J. Blagg,&nbsp;Kun Zou,&nbsp;Michael S. Wolfe","doi":"10.1111/jnc.70544","DOIUrl":"https://doi.org/10.1111/jnc.70544","url":null,"abstract":"<p>Deposition of amyloid β-protein (Aβ) is a hallmark of Alzheimer's disease (AD), produced by γ-secretase–mediated cleavage of amyloid precursor protein (APP). The 90-kDa heat shock protein (Hsp90) co-chaperone, activator of Hsp90 ATPase homolog 1 (AHA1), is known to promote the accumulation of toxic tau species; however, its effects on Aβ production remain unclear. Using cellular models—including human embryonic kidney 293 T (HEK293T) cells, stable HEK-APP cells, presenilin 1/2 double-knockout mouse embryonic fibroblasts (PS-DKO MEFs), and Chinese hamster ovary (CHO) cells—in which AHA1 was experimentally manipulated, together with observational analyses of human iPSC-derived neurons carrying an FAD-linked APP mutation, we demonstrate that AHA1 regulates Aβ generation through two mechanisms: regulation of APP protein abundance through pathways that are at least partially independent of Hsp90 interaction and Hsp90-dependent promotion of γ-secretase assembly. Knockdown of endogenous AHA1 reduces Aβ production and decreases APP and γ-secretase component levels, whereas AHA1 overexpression elevates Aβ generation and increases the expression of these proteins. The AHA1-E67K mutant, which has impaired Hsp90 binding, lowers Aβ production and the levels of APP and γ-secretase components compared with wild-type AHA1. AHA1 associates with APP and APH1, an immature γ-secretase component, indicating its role in APP proteolysis and Aβ production. Disruption of the AHA1/Hsp90 complex—through AHA1 knockdown, the E67K mutant, or a small-molecule inhibitor—reduces γ-secretase assembly. Notably, Familial AD mutations (APP-C99-I45F, PS1-L286V) upregulate AHA1/Hsp90, elevating APP/APH1 and Aβ42 production. AHA1 knockdown rescues FAD-linked Aβ42 overproduction in a mutant cell model, while AHA1 overexpression exacerbates PS1 mutant Aβ production. Collectively, these findings reveal that AHA1 regulates Aβ production by modulating APP abundance and γ-secretase assembly, establishing AHA1 as a potential target for therapeutic intervention in AD.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70544","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Varicose Projection Astrocytes: Not a Cell Type, but a Cell State","authors":"Carmen Falcone,&nbsp;Alexei Verkhratsky","doi":"10.1111/jnc.70542","DOIUrl":"10.1111/jnc.70542","url":null,"abstract":"&lt;p&gt;Idiosyncratic astrocytes distinguish human brain from other mammals and even primates. Human protoplasmic and fibrous astrocytes are much larger and more complex (Oberheim et al. &lt;span&gt;2009&lt;/span&gt;) compared to other mammals. Arguably astrocytes underwent major change in the course of evolution from apes to man (Ciuba et al. &lt;span&gt;2025&lt;/span&gt;). In addition, human brain contains several types of astrocytes (most notably interlaminar astrocytes) which show a higher morphological complexity and higher density in hominid primates compared to other mammals including rodents mainly used in laboratory experiments (Colombo and Reisin &lt;span&gt;2004&lt;/span&gt;; Falcone et al. &lt;span&gt;2019&lt;/span&gt;). The varicose projection astrocytes are another cell type that was generally considered to be uniquely possessed by the brain of hominoids (Falcone et al. &lt;span&gt;2021&lt;/span&gt;; Oberheim et al. &lt;span&gt;2009&lt;/span&gt;). These cells were first cataloged in the deep cortical layers and white matter of humans and other great apes. Their name reflects their morphology: these astrocytes extend long GFAP-positive processes with evenly spaced, bead-like swellings (termed varicosities) that cross other astrocytes territory disrespecting territorial domains characteristic of protoplasmic astrocytes. Because they had been reported only in hominoids (Falcone et al. &lt;span&gt;2021&lt;/span&gt;; Oberheim et al. &lt;span&gt;2009&lt;/span&gt;), varicose projection astrocytes were classified into a growing list of hominoid astrocytic specializations and treated, by default, as a physiological cell type with function awaiting discovery.&lt;/p&gt;&lt;p&gt;That assumption however was at odds with data accumulating in recent years. First and foremost, varicose projection astrocytes were found not only in primates but throughout mammals from rodents to Felidae, in ferret, pig and even the goat (Ciani et al. &lt;span&gt;2026&lt;/span&gt;; Oyadeyi et al. &lt;span&gt;2026&lt;/span&gt;; Tai et al. &lt;span&gt;2024&lt;/span&gt;), thus dismantling the premise that this phenotype is hominoid-restricted (Figure 1). Furthermore, the varicose projection appeared inconsistently throughout individuals of the same species (they were present in some individuals of a species but not others) and was always accompanied by the presence of varicosities in other astrocyte subtypes (like the interlaminar astrocytes) (Falcone et al. &lt;span&gt;2021&lt;/span&gt;), suggesting that their presence was linked to specific status of the brain. Finally, as was discovered very recently (Ciani et al. &lt;span&gt;2026&lt;/span&gt;), the presence of varicose projection astrocytes correlated either with an advanced age or with diseases, suggesting a pathological association. Indeed, the varicose projection astrocytes can be induced by modeling diverse pathologies. In particular, exposing human iPSC-derived astrocytes and mouse ESC-derived astrocytes to the pro-inflammatory cytokines IL-1β and TNF-α, as well as treating human organoids with LPS acting through microglia, all resulted in a significant increase in the density of v","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148818446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Unconventional Protein Secretion in the Central Nervous System: Mechanisms and Roles in Physiology and Disease”","authors":"","doi":"10.1111/jnc.70545","DOIUrl":"10.1111/jnc.70545","url":null,"abstract":"<p>\u0000 <span>Krauklis, S. A.</span>, <span>S. K. Keçeli</span>, <span>E. M. Campbell</span>, and <span>P. S. Abbineni</span>. <span>2026</span>. “ <span>Unconventional Protein Secretion in the Central Nervous System: Mechanisms and Roles in Physiology and Disease</span>.” <i>Journal of Neurochemistry</i> <span>170</span>, no. <span>7</span>: e70532. https://doi.org/10.1111/jnc.70532.\u0000 </p><p>The last sentence of the Abstract currently reads: “Finally, we discuss key unresolved question Recent evidence from HeLa cells suggests regarding the regulation of UcPS, including the molecular features that target select leaderless cargoes toward UcPS, how the balance between conventional secretion and UcPS shifts under cellular stress, and the current understanding of the diverse molecular machinery that mediates the vesicular form of UcPS.” The phrase “Recent evidence from HeLa cells suggests” was included erroneously. The sentence should instead read: “Finally, we discuss key unresolved questions regarding the regulation of UcPS, including the molecular features that target select leaderless cargoes toward UcPS, how the balance between conventional secretion and UcPS shifts under cellular stress, and the current understanding of the diverse molecular machinery that mediates the vesicular form of UcPS.”</p><p>We apologize for this error.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal Astrocytes Impact Postnatal Development of Inhibitory Connections, Parvalbumin Levels, Social, and Spatial Navigation Behaviors in a Mouse Model of Fragile X Syndrome","authors":"Victoria A. Wagner,&nbsp;Sarah Maples,&nbsp;Ritika Thapa,&nbsp;Jordan Wimberly,&nbsp;Ellie Pettijohn,&nbsp;Alexandra Varallo,&nbsp;Maham Rais,&nbsp;Samantha Sutley-Koury,&nbsp;Peter Hickmott,&nbsp;Iryna M. Ethell","doi":"10.1111/jnc.70541","DOIUrl":"10.1111/jnc.70541","url":null,"abstract":"<p>Fragile X Syndrome (FXS) is a leading genetic cause of autism-like symptoms and intellectual disability, resulting from epigenetic silencing of the <i>Fragile X messenger ribonucleoprotein (Fmr1) gene</i>. Recent observations in FXS models suggest abnormal GABAergic signaling and excitation/inhibition imbalance may underlie the pathophysiology of FXS. As most studies have focused on neuronal mechanisms, the role of astrocytes in mediating defective inhibition in FXS is largely unknown. Our previous study showed the effects of astrocyte-specific <i>Fmr1</i> conditional knockout (cKO) on cortical inhibitory circuit development using EEGs that were attributed to excess GABA synthesis by <i>Fmr1</i> KO astrocytes. As the hippocampus plays an important role in spatial learning and social behaviors that are altered in FXS, in this study we focused on dissecting the mechanism of abnormal inhibition in the CA1 hippocampus using slice electrophysiology. While we observed a reduction in the expression of synaptic GABA_A receptor subunits and overall density of perisomatic GABAergic synapses in cKO, the amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) was enhanced in pyramidal cells. In contrast to changes in phasic inhibition, astrocyte-specific cKO did not affect tonic inhibition in pyramidal cells or the expression of extrasynaptic GABA_A receptors, which were both impaired in global KO. Our study suggests that elevated levels of extracellular GABA due to abnormal GABA transport in cKO astrocytes may contribute to the enhanced power of sIPSCs and potentially affect parvalbumin (PV) cell activity. Acute inhibition of GABA transport in astrocytes enhanced PV expression and improved spatial memory and socialization in cKO mice. Our work supports astrocytes as key players in the development and regulation of hippocampal inhibitory circuits in FXS, potentially through GABA transport.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estradiol Replacement Modulates Synaptic Transmission-Related Proteins in the Hippocampus of Ovariectomized Rats: An Exploratory Proteomic Approach","authors":"Amanda Paula Pedroso,&nbsp;Adriana Pereira Souza,&nbsp;Guilherme Araújo Câmara,&nbsp;Meira Maria Forcellini Machado,&nbsp;Valter Tadeu Boldarine,&nbsp;Lila Missae Oyama,&nbsp;Mônica Marques Telles,&nbsp;Alexandre Keiji Tashima,&nbsp;Eliane Beraldi Ribeiro","doi":"10.1111/jnc.70536","DOIUrl":"https://doi.org/10.1111/jnc.70536","url":null,"abstract":"<p>The loss of ovarian hormones in postmenopause influences cognition, emotion and energy homeostasis, processes integrated by the hippocampus. The mechanisms by which estradiol influences this area have not been fully understood. The present study aimed at investigating the effects of estradiol on the rat hippocampus proteome of ovariectomy-induced menopause either followed by estradiol replacement or not. Eighteen 3-month-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 months. A subgroup of ovariectomized rats received estradiol replacement. The hippocampi were processed using data independent acquisition MS-based proteomics and differentially expressed proteins were submitted to bioinformatics analysis for a pathway-based functional understanding of the estradiol effects. Proteomic analysis revealed that 49 hippocampal proteins were modulated by ovariectomy and estradiol replacement. Functional analysis of the differentially expressed proteins revealed the enrichment of terms related to energy metabolism (comprising glycolysis/gluconeogenesis, pyruvate metabolism, oxidative phosphorylation, and response to oxidative stress) and neuron projection (comprising cytoskeleton organization, regulation of vesicle-mediated transport, and modulation of chemical synaptic transmission). The present dataset indicates that, at the hippocampus, estradiol affects mitochondrial dynamics, lipid metabolism and intracellular trafficking machinery and influences dendritic and synaptic transmission and brain plasticity. Some alterations observed in proteins have not yet been described in the hippocampus in the context of menopause and estradiol replacement. These data provide new insights into the mechanisms involved with menopause effects and may help future studies related to drug development for the prevention and treatment of postmenopause associated symptoms.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Adrenal Medulla Activity in Germ-Free Versus Conventional Male Rats Under Acute and Chronic Stress","authors":"Camille Etienne,&nbsp;Claire Bernat,&nbsp;Magali Monnoye,&nbsp;Virginie Andry,&nbsp;Catherine Philippe,&nbsp;Claire Maudet,&nbsp;Elise Maximin,&nbsp;Laurent Naudon,&nbsp;Yannick Goumon,&nbsp;Christine Heberden,&nbsp;Nathalie C. Guérineau,&nbsp;Sylvie Rabot","doi":"10.1111/jnc.70538","DOIUrl":"https://doi.org/10.1111/jnc.70538","url":null,"abstract":"<p>It has now been well established that gut microbiota significantly influences emotional and neuroendocrine responses to stress. Specifically, multiple pieces of evidence from various preclinical models indicate that gut microbiota regulates the response of the hypothalamic–pituitary-adrenocortical (HPA) axis to acute and chronic stress. In contrast, the influence of gut microbiota on the adrenomedullary tissue, which is responsible for the production and release of catecholamines—the first hormones released in response to stress—has received little attention. Therefore, our study aimed to explore whether adrenal corticosterone and catecholamine biosynthesis were differently regulated in germ-free (GF) and conventional, specific pathogen-free (SPF) male rats when exposed to unpredictable chronic mild stress, acute metabolic stress, or both. Results showed that both GF and SPF chronically stressed rats had significantly (<i>p</i> &lt; 0.05) heavier adrenal glands (+30% for GF, +21% for SPF) compared to unstressed animals. Gene expression levels of corticosterone biosynthesis enzymes and plasma and adrenal corticosterone concentrations did not differ significantly between control rats and those exposed to chronic, acute, or both stress factors, whether in GF or SPF rats. The same result was observed for the genes encoding tyrosine hydroxylase and dopamine β-hydroxylase, two enzymes involved in catecholamine biosynthesis. By contrast, GF rats exhibited a 2.3-fold increase (<i>p</i> = 0.0271) in <i>Pnmt</i> gene expression (which encodes phenylethanolamine N-methyltransferase, the enzyme responsible for converting norepinephrine to epinephrine) and a 2.6-fold increase (<i>p</i> = 0.0786) in epinephrine concentration in the adrenal glands under combined stress conditions. This response was not observed in SPF rats. In these animals, chronic stress was found to reshape the composition and metabolic functions of the gut microbiota. Interestingly, this was accompanied by a 40% decrease in norepinephrine (<i>p</i> = 0.0364) and epinephrine (<i>p</i> = 0.0840) concentrations in their adrenal glands. This study highlights the gut microbiota as a regulator of adrenomedullary activity, enhancing our understanding of the interaction between peripheral and central stress circuitry.</p><p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jnc.70538","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium-Dependent Cytoskeletal Collapse and Recovery of Axons After Partial Laser Ablation","authors":"Ashish Mishra,&nbsp;Pooja Joshi,&nbsp;Md Arsalan Ashraf,&nbsp;Pramod Pullarkat","doi":"10.1111/jnc.70539","DOIUrl":"10.1111/jnc.70539","url":null,"abstract":"<div>\u0000 \u0000 <p>Traumatic stretch or crush injury to axons causes widespread and often irreversible damage to the axonal cytoskeleton, in which calcium-mediated breakdown is known to play a central role. Unlike complete transection, where recovery must proceed through formation of a new growth cone, milder injury can disrupt the axonal cytoskeleton while leaving the plasma membrane intact. How the cytoskeleton fails, and how it can recover, under these conditions remains unclear. Here we address this using a partial laser-ablation method that damages the cytoskeleton and evokes a calcium transient while preserving membrane continuity. We show that the ensuing cytoskeletal retraction is set by a mechanical balance between acto-myosin contractility and microtubule stability: stabilizing microtubules or inhibiting acto-myosin contractility suppresses retraction. Moreover, chelating extracellular calcium mitigates degeneration and, in a subset of axons, permits complete recovery. We also show that microtubules and actin filaments show distinct loss and recovery dynamics and provide a hypothesis for the “burning-fuse” -like depolymerization of the microtubule bundle. These findings provide insights into how the axonal cytoskeleton collapses and recovers after injury and suggest strategies for mitigating damage.</p>\u0000 <p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>\u0000 </div>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":"170 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712777","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}