CNS Neuroscience & Therapeutics最新文献

{"title":"Development, Optimization, and Physicochemical Characterization of Fluorescent Carbon Dot-Ginkgo biloba Extract Co-Loaded Niosomes for Future Neurological Disease-Relevant Evaluation","authors":"Yasaman Mohammadi,&nbsp;Mohammad Saied Salehi,&nbsp;Ehsan Heidari,&nbsp;Mina Ebrahimi,&nbsp;Nahid Ashjazadeh","doi":"10.1002/cns.71230","DOIUrl":"https://doi.org/10.1002/cns.71230","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is one of the major neurodegenerative diseases that affect the human brain and lead to memory loss. The present approaches to disease management have been relatively poor; the therapies provided do not arrest the disease process. This study aimed to develop and optimize dual-loaded niosomes containing <i>Ginkgo biloba</i> extract and CDOTs and to evaluate their physicochemical properties, formulation-level fluorescence, in vitro release, and preliminary cytocompatibility. The study did not assess blood–brain barrier transport, neuronal effects, Alzheimer's disease-specific mechanisms, or in vivo therapeutic efficacy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Niosomes were prepared based on non-ionic surfactants and cholesterol for the encapsulation of Ginkgo and CDOTs. The response surface methodology (RSM) was used to optimize niosomal formulations through a Box–Behnken design. The formulations were evaluated for vesicle size, entrapment efficiency, and release profile. Field Emission Scanning Electron Microscopy (FESEM) research indicated that the average diameters of the free niosomes and CDOT@Ginkgo@Niosomes were 69.56 nm and 72.19 nm, respectively. HFF cell viability remained high at lower concentrations, whereas significant reductions in viability were observed at 10 and 50 μg/mL after 48 h, indicating concentration-dependent cytocompatibility. The formulation exhibited acceptable preliminary cytocompatibility at lower concentrations, whereas reduced viability was observed at higher concentrations. For both CDOT and Ginkgo, CDOT@Ginkgo@Niosomes showed a delayed release profile over 72 h, with near-complete release observed at the final time point.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CDOT@Ginkgo@Niosomes showed successful co-loading, preserved formulation-level fluorescence, delayed release, and acceptable cytocompatibility at lower concentrations in HFF cells. These findings support further formulation optimization and subsequent evaluation in disease-relevant neuronal, blood–brain barrier, and in vivo models. The present results do not demonstrate neuroprotection, diagnostic performance, blood–brain barrier transport, or the prevention or treatment of neurodegenerative disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71230","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morinda Officinalis Oligosaccharides Alleviate Post-Stroke Depression-Like Behaviors Alongside Increased Gut Microbial Diversity and Butyrate Levels and Reduced Hippocampal Pla2g4a Expression","authors":"Hui Ma,&nbsp;Yue Chen,&nbsp;Xinzhou Deng,&nbsp;Xuan Fang,&nbsp;Wenhui Xiao,&nbsp;Qian Long,&nbsp;Lu Du,&nbsp;Fuze Du,&nbsp;Haonan Chen,&nbsp;Yan Wang,&nbsp;Bo Gao,&nbsp;Xin Qiao","doi":"10.1002/cns.71238","DOIUrl":"10.1002/cns.71238","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background and Purpose&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Post-stroke depression (PSD) represents a common and debilitating complication after cerebral ischemia, yet mechanism-based therapies remain an urgent unmet need. The microbiota-gut-brain axis has been implicated in PSD pathophysiology, but the precise molecular pathways are largely elusive. Morinda officinalis oligosaccharides (MOO), a clinically approved antidepressant in China, exhibit poor oral absorption, raising the possibility of a gut-dependent mechanism.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Experimental Approach&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Male C57BL/6J mice were subjected to transient middle cerebral artery occlusion (MCAO) followed by 21 days of chronic restraint stress (CRS) to establish a PSD model. MOO (50 mg/kg/day) was administered via gavage from Day 7 to 27. Depression-like behaviors, 16S rRNA-based gut microbiota profiling, short-chain fatty acid (SCFA) quantification, intestinal and blood–brain barrier integrity assessments, and hippocampal proteomics were performed. The transferability of MOO-associated fecal effects was assessed using a donor-controlled fecal microbiota transplantation (FMT) design. The butyrate-Pla2g4a relationship was further examined by sodium butyrate supplementation and AAV-mediated hippocampal Pla2g4a overexpression.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;MOO administration altered gut microbial composition, increased the abundance of probiotics and decreased the abundance of harmful bacteria, and was accompanied by increased fecal butyrate levels. The donor-controlled FMT experiment provided preliminary evidence that fecally transferable factors from MOO-treated PSD donors may contribute to behavioral improvements in PSD recipients. MOO and sodium butyrate treatment were associated with improved indices of intestinal and blood–brain barrier integrity. Hippocampal proteomics identified Pla2g4a, a phospholipase linked to neuroinflammation, as a candidate molecule related to the observed effects. Both MOO and sodium butyrate treatment were associated with reduced hippocampal Pla2g4a expression, and Pla2g4a expression was inversely correlated with butyrate levels. Hippocampal Pla2g4a overexpression attenuated the behavioral improvements associated with sodium butyrate treatment, supporting the functional involvement of Pla2g4a in the response to sodium butyrate.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions and Implications&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;MOO treatment was associated with improved depression-like behaviors in PSD mice, accompanied by gut microbial alterations, increased fecal butyra","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ixodes ricinus-Contact Phase Inhibitor Promotes Functional Recovery and Attenuates Neutrophil Associated Neuroinflammation After Experimental Intracerebral Hemorrhage","authors":"Stéphanie Demoulin,&nbsp;Annelise Letourneur,&nbsp;Florent Lebrun,&nbsp;Nicolas Violle,&nbsp;Denis Vivien,&nbsp;Valérie Pireaux","doi":"10.1002/cns.71227","DOIUrl":"10.1002/cns.71227","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Neutrophil-associated inflammation contributes to secondary brain injury after intracerebral hemorrhage (ICH). We evaluated whether <i>Ixodes ricinus</i>-Contact Phase Inhibitor (Ir-CPI), a selective factor XIa/XIIa inhibitor with reported thromboinflammatory modulatory properties, improves outcome after experimental ICH without worsening bleeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a collagenase-induced mouse ICH model, Ir-CPI was administered as an intravenous bolus followed by a 3-day infusion. Vehicle animals served as controls and enoxaparin as an anticoagulant comparator. Cohorts evaluated hemorrhage and lesion volumes, endothelial activation, neutrophil-associated inflammation, and longitudinal functional recovery. Ir-CPI association with human neutrophils was evaluated in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ir-CPI did not increase hemorrhage or lesion volumes versus PBS through Day 14, whereas enoxaparin showed a higher Day 1 hemorrhage volume than Ir-CPI. Flow cytometry showed Ir-CPI association with human neutrophils. In the mouse model, Ir-CPI produced region-specific reductions in neutrophil infiltration and NET formation and reduced neuronal degeneration at the injection site and caudal level, without affecting VCAM-1-associated endothelial activation. Ir-CPI accelerated functional recovery, improving neurological scores and sensorimotor asymmetry by Day 5, with restoration of baseline corner test performance by Day 14.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ir-CPI improves recovery after experimental ICH without exacerbating bleeding and is associated with reduced neutrophil-associated secondary brain injury. These findings support its translational potential as a therapeutic strategy for ICH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Lipidomic Features of Adolescent Major Depressive Disorder and Lipid Changes After Fluoxetine Treatment","authors":"Chenxi Liu,&nbsp;Yao Li,&nbsp;Hanchen Hou,&nbsp;Jiamei Guo,&nbsp;Bingjie Qin,&nbsp;Xiaoxia Xu,&nbsp;Yuqian He,&nbsp;Tingting Lei,&nbsp;Fei Chen,&nbsp;Lige Zhang,&nbsp;Quanbing Liu,&nbsp;Li Gao,&nbsp;Jiaqi Shi,&nbsp;Haoran Xing,&nbsp;Teng Teng,&nbsp;Tian Qiu,&nbsp;Xinyu Zhou","doi":"10.1002/cns.71202","DOIUrl":"10.1002/cns.71202","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Major depressive disorder (MDD) in adolescents is a major public health concern, yet objective biological markers and treatment-related metabolic changes remain insufficiently understood. This study aimed to characterize plasma lipidomic alterations in adolescent MDD and explore lipid changes associated with fluoxetine treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study enrolled 75 adolescents with MDD and 75 matched healthy controls (HCs). Among the adolescents with MDD, 44 had paired baseline and week-8 plasma samples available and were included in the longitudinal analysis. Plasma lipidomic profiles were analyzed using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 865 lipid species were detected. Compared with HCs, adolescents with MDD showed distinct plasma lipidomic profiles, with 82 differentially abundant lipid species identified, primarily involving triglycerides, lysophospholipids, free fatty acids, membrane phospholipids, and sphingolipids. Among the machine-learning models, logistic regression showed the highest discriminative performance, with a pooled out-of-fold AUC of 0.85 (95% CI, 0.79–0.91). Longitudinal analysis identified 21 lipid species meeting the differential criteria following fluoxetine treatment, mainly involving triglycerides and bile acid-related metabolites. Integrative pathway and target analyses suggested that fluoxetine-associated lipid changes may involve neurotransmitter signaling, inflammatory lipid metabolism, PI3K–Akt signaling, and nuclear receptor-related pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study characterizes alterations in plasma lipid metabolism in adolescent MDD and the lipidomic changes following fluoxetine treatment, providing new lipidomic evidence for candidate lipid signatures and potential treatment-associated biological pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov, NCT05814640. Registered 20 February 2023, https://clinicaltrials.gov/study/NCT05814640</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Locations for Noninvasive Brain Stimulation in Treating Poststroke Deficits: Exploration From Multimodal Neuroimaging","authors":"Sitong Yuan,&nbsp;Yue Yang,&nbsp;Yi Han,&nbsp;Ying Gao,&nbsp;Jingling Chang,&nbsp;Huize Lin,&nbsp;Jinna Yu,&nbsp;Binlong Zhang","doi":"10.1002/cns.71229","DOIUrl":"10.1002/cns.71229","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Noninvasive brain stimulation (NIBS) shows promise for poststroke deficits (PSDs), but efficacy may be limited by inconsistent stimulation sites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By integrating neuroimaging meta-analysis, lesion-symptom mapping (LSM), and resting-state functional connectivity (FC) analysis, we employed three analytical pipelines to explore potential NIBS targets for alexia, aphasia, apraxia, ataxia, dysarthria, hemiplegia, paresthesia, and dysphagia. Pipeline 1 identified cortical regions directly associated with each PSD via coordinate-based meta-analysis using Neurosynth Compose. Pipeline 2 identified cortical regions exhibiting maximal functional connectivity with neurosynth-derived regions of interest (ROI). Pipeline 3 identified cortical regions functionally connected to ROIs from a prior large-scale LSM study. During Pipeline 2 and 3, ROIs were used for seed-to-voxel FC analysis using resting-state fMRI data from 100 healthy subjects. Identified cortical targets were mapped onto the scalp and referenced by the 10–20 system and continuous proportional coordinates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Potential cortical targets and scalp locations were identified for all eight PSDs. For instance, for hemiplegia, validated targets included primary motor and somatosensory cortices and supplementary motor area; novel targets included angular gyrus, superior frontal gyrus, inferior parietal lobule, medial prefrontal cortex, and precuneus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This multimodal approach systematically identified precise NIBS targets, confirming established sites and revealing novel regions to broaden neuromodulation strategies for poststroke recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic Reticulum Autophagy Enhancement Alleviates Synaptic Plasticity Dysfunction and Ameliorates Cognitive Impairment in SAE Mice by Relieving STING-Associated Inhibition of PKM2 Activity","authors":"Xiaofeng Guo,&nbsp;Daqing Yin,&nbsp;Zhonghua Zhang,&nbsp;Yuanyuan Zhao,&nbsp;Yali Zhang,&nbsp;Ying Jiang,&nbsp;Zhanying Zhao,&nbsp;Tongwen Sun,&nbsp;Feihu Zhou,&nbsp;Xijing Zhang","doi":"10.1002/cns.71233","DOIUrl":"10.1002/cns.71233","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The pathogenesis of cognitive impairment in patients with sepsis-associated encephalopathy (SAE) remains unclear. This study investigated whether enhancing micro-endoplasmic reticulum autophagy (micro-ER-phagy) could alleviate synaptic dysfunction and improve cognitive impairment in SAE mice models by relieving stimulator of interferon gene (STING)-associated inhibition of pyruvate kinase M2 (PKM2) activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male wild-type and neuron-specific PKM2 conditional knockout mice (<i>PKM2</i>^fl/fl; hSyn-Cre⁺) were used. Cognitive function in SAE mice models was assessed using the Y-maze and contextual fear conditioning tests. Neuronal plasticity was examined using transmission electron microscopy and Golgi staining, whereas immunofluorescence staining and Western blotting were employed to determine the temporal and spatial expression patterns of related proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Septic mice developed cognitive impairment. Hippocampal tissues of SAE mice exhibited synaptic plasticity dysfunction and glycolysis enhancement. Meanwhile, the hippocampus showed increased PKM2 expression and an altered ratio of PKM2 tetramers and dimers. In addition, phosphorylated STING significantly increased in concentration in hippocampal neurones and its knockdown improved cognitive function. However, this cognitive rescue failed in PKM2 conditional knockout mice treated with SAE. Finally, Sec62-mediated micro-ER-phagy promoted lysosomal degradation of STING, which relieved STING-mediated inhibition of PKM2 and improved synaptic plasticity and cognitive dysfunction in SAE mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated micro-ER-phagy may relieve the STING-associated inhibition of PKM2 activity, improve neuronal glycolysis and synaptic plasticity, and alleviate cognitive dysfunction in SAE mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 11","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149293504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAFG as a Redox-Sensitive Node Linking Peripheral Immune Reprogramming to Cognitive Risk in the Sepsis-to-Alzheimer's Disease Continuum: Single-Cell Dissection and Adoptive-Transfer Validation","authors":"Xiaoyu Xiang,&nbsp;Tingting Li,&nbsp;Zhongxue Feng,&nbsp;Jing Yang,&nbsp;Zhiwen Gong,&nbsp;Lietao Wang,&nbsp;Lijun Wang,&nbsp;Wei Zhang","doi":"10.1002/cns.71201","DOIUrl":"10.1002/cns.71201","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis survivors face an elevated long-term risk of Alzheimer's disease (AD), yet the peripheral pathways linking systemic immune activation to chronic neurodegeneration remain undefined. We mapped peripheral immune reprogramming across sepsis and AD and tested a candidate regulatory node.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-cell atlas of peripheral immunity was built by integrating scRNA-seq from human sepsis and AD cohorts, using clustering, SCENIC regulatory-network inference and an exploratory pseudotime ordering. The resulting signature was validated in two clinical cohorts (ROC and survival analysis). MAFG-associated subpopulations and redox status were profiled in APP/PS1, cecal ligation and puncture (CLP) and composite models, and causality was tested by lentiviral MAFG knockdown and adoptive transfer into APP/PS1 recipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Peripheral immunity was myeloid-skewed in sepsis and lymphoid-dominated in AD, with APP-expressing common myeloid progenitors (CMPs), dendritic cells (DCs), and platelets forming an APP-enriched compartment. A core transcription-factor network differed between disease states, yielding a four-gene signature (MAFG, NFIL3, RGS10, FOXO3) with cross-cohort diagnostic and prognostic value. MAFG was upregulated in septic patients and associated with poorer survival, subpopulation expansion, and systemic oxidative stress. Superimposed CLP aggravated amyloid deposition, microglial activation, and memory deficits in APP/PS1 mice, whereas MAFG silencing restored Aβ uptake and, on adoptive transfer, reduced amyloid burden, attenuated microgliosis, and preserved cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Peripheral immune states differ across the sepsis-to-AD spectrum and are captured by a MAFG-centered signature. Independent of any trajectory assumption, loss-of-function and adoptive-transfer experiments identify MAFG as a causal, redox-sensitive node constraining peripheral Aβ clearance and a candidate biomarker and therapeutic target in sepsis survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction Between Peripheral Cytokines and Central Neuroinflammation in Temporal Lobe Epilepsy","authors":"Heyu Zhang,&nbsp;Ningning Wang,&nbsp;Yuying Zhang,&nbsp;Siqi Ou,&nbsp;Jingjing Chen,&nbsp;Jinming Zhang,&nbsp;Yicong Liu,&nbsp;Yuting Luo,&nbsp;Yingting Luo,&nbsp;Ziheng Wei,&nbsp;Kailin Wu,&nbsp;Xiangsong Zhang,&nbsp;Ziyi Chen,&nbsp;Guanzhong Ni","doi":"10.1002/cns.71200","DOIUrl":"https://doi.org/10.1002/cns.71200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Neuroinflammation is a key pathogenic mechanism in temporal lobe epilepsy, quantifiable in vivo using positron emission tomography targeting the translocator protein. This study integrated [¹⁸F]DPA-714 PET/MRI with serum cytokine profiling to investigate this central–peripheral immune relationship in TLE patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective study of 24 TLE patients and 24 healthy controls (HCs) was conducted. PET/MRI data were available for 24 TLE patients and 7 HCs, while cytokine data were available for all 24 participants in both groups. Standardized uptake value ratios of [¹⁸F]DPA-714 were calculated for key temporal lobe regions. Serum levels of IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ were quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with HCs, TLE patients demonstrated significantly increased [¹⁸F]DPA-714 PET/MRI uptake in ipsilateral temporal lobe structures (group main effect: <i>F</i>_1,29 = 15.779, <i>p</i> &lt; 0.001), accompanied by a proinflammatory serum profile with elevated IL-17 and IFN-γ and decreased IL-2, IL-4, and IL-10 levels (<i>p</i> &lt; 0.05). Ipsilateral hippocampal [¹⁸F]DPA-714 SUVR was positively correlated with disease duration (<i>ρ</i> = 0.46, <i>p</i> = 0.025) and seizure frequency (<i>ρ</i> = 0.52, <i>p</i> = 0.018). However, no significant associations were observed between neuroimaging-assessed central neuroinflammation and serum cytokines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>[¹⁸F]DPA-714 PET/MRI precisely demonstrates focal neuroinflammation in TLE patients, correlating with clinical severity, yet the lack of correlation with peripheral markers highlights that peripheral and central immune responses represent distinct and relatively independent inflammatory processes in TLE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetylation-like H2BK109Q attenuates acute brain injury and preserves axon-myelin integrity after intracerebral hemorrhage","authors":"Sinan Jin,&nbsp;Meng Yang,&nbsp;Jincheng Meng,&nbsp;Ziyi Han,&nbsp;Yousef Rastegar-Kashkooli,&nbsp;Pengtian Lu,&nbsp;Junmin Wang,&nbsp;Jian Wang,&nbsp;He Wu","doi":"10.1002/cns.71172","DOIUrl":"10.1002/cns.71172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Axon–myelin damage contributes to neurological dysfunction after intracerebral hemorrhage (ICH), but the upstream chromatin regulators remain unclear. We aimed to characterize the H2B acetylation response to ICH, test the functional significance of modeled H2BK109 states, and identify a downstream effector of H2BK109Q-mediated protection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pan-H2B acetylation was examined in mice with collagenase-induced ICH and in hemoglobin-treated HT22 cells, and the histone acetylome of the mouse brain was profiled. H2BK109Q and H2BK109R were used to model acetylation-mimetic and non-acetylated lysine-like states. Injury outcomes, axon–myelin integrity, molecular profiles, and regional Galc knockdown were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ICH and hemoglobin reduced pan-H2B acetylation, and acetylome profiling indicated reduced H2BK109ac. H2BK109Q-expressing mice showed higher pan-H2B acetylation, smaller hematomas, less edema and apoptosis, improved neurological function, and greater preservation of LFB, MBP, NF200, and axon–myelin ultrastructure. Under matched hemoglobin exposure, H2BK109Q-expressing HT22 cells showed higher BCL2/BAX ratios and lower TUNEL positivity than H2BK109R-expressing cells. In vitro analyses highlighted GALC as a candidate downstream effector of H2BK109Q-associated protection. In H2BK109Q-expressing mice, Galc knockdown reduced LFB- and MBP-positive areas and NF200 signals in the caudate putamen and corpus callosum compared with untreated and siNC controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>H2BK109Q attenuates acute ICH injury and preserves axon–myelin integrity, with GALC contributing to these protective effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Reproductive Factors and Postmenopausal Sex Hormones With Cognitive Impairment in Postmenopausal Women With Parkinson's Disease","authors":"Wen-Zheng Hu,&nbsp;Qin Wang,&nbsp;Ling Tang,&nbsp;Jia-Qi Wang,&nbsp;Di Hu,&nbsp;Teng-Teng Wu,&nbsp;Yue Huang,&nbsp;Zhi-Hong Shi,&nbsp;Yi Ren,&nbsp;Zhi-Rong Wan,&nbsp;Ping-Yi Xu","doi":"10.1002/cns.71182","DOIUrl":"10.1002/cns.71182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To explore the associations of reproductive factors (RFs) and postmenopausal sex hormone (PSH) with cognitive impairment (CI) in postmenopausal women with PD (PWPD), and to develop a predictive nomogram.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ninety-five PWPD were divided into CI (<i>n</i> = 72; Montreal Cognitive Assessment [MoCA] &lt; 26) and normal cognition (<i>n</i> = 23; MoCA ≥ 26) groups. RFs and serum PSH levels were collected. Risk factors were screened by logistic regression and confirmed via sensitivity and subgroup analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Shorter reproductive lifespan (RLS) and lower education independently predicted CI in PWPD. Compared with RLS ≥ 39 years, RLS ≤ 32 years (adjusted OR = 12.41, <i>p</i> = 0.011) and 33–38 years (adjusted OR = 8.42, <i>p</i> = 0.008) were associated with significantly higher CI risks. The RLS-CI association remained stable across sensitivity analyses and was more prominent in milder-stage patients. No intergroup PSH differences were observed. A nomogram integrating RLS, education, age, disease duration, and Hoehn and Yahr stage (H&amp;Y stage) demonstrated satisfactory discrimination (AUC = 0.903), calibration, and net benefit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Shorter RLS independently predicts CI in PWPD, particularly in milder-stage patients, while PSH shows no association. This nomogram may serve as a practical screening tool for CI in PWPD, pending external validation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}