CNS Neuroscience & Therapeutics最新文献

{"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}

{"title":"Metabolomics Analysis Revealed That SXZ Ameliorates Cognitive Impairment in Naturally Aged Rats by Promoting Glutathione Metabolism and Inhibiting the Ferroptosis Pathway","authors":"Mengya Liu,&nbsp;Shunyi Li,&nbsp;Yonglin Liang,&nbsp;Yugui Zhang,&nbsp;Xutong Jia,&nbsp;Yongqiang Duan,&nbsp;Min Bai","doi":"10.1002/cns.71194","DOIUrl":"10.1002/cns.71194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to examine the potential neuroprotective effects of SXZ on cognitive impairment in naturally aging rats and to explore the underlying molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighteen-month-old Sprague–Dawley rats were used as a natural aging model and administered Shenxian Zhou (SXZ) for 6 months. Cognitive function was assessed using behavioral evaluations. Hematoxylin–eosin, Nissl, and immunofluorescence staining for NeuN were performed to evaluate neuronal pathology in aging rats. Metabolomics analysis was performed to characterize hippocampal metabolites, followed by molecular validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SXZ attenuated age-related cognitive decline and reduced hippocampal pathological and neuronal damage in naturally aging rats. SXZ-H significantly modulated glutathione metabolism and ferroptosis-associated signaling pathways. Transmission electron microscopy revealed mitochondrial morphological changes consistent with ferroptosis in hippocampal neurons of naturally aging rats. Molecular biology experiments further indicated that, subsequent to SXZ-H intervention, lipid peroxidation and oxidative stress levels were significantly reduced. Furthermore, expression levels of p53 and Keap1 genes and proteins were significantly downregulated, whereas the expression of SLC7A11, GPX4, Nrf2, and HO-1 genes and proteins was notably upregulated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SXZ-H effectively mitigates cognitive impairment in naturally aging rats, an effect that may be mediated by promoting glutathione metabolism and regulating key ferroptosis-related proteins, thereby inhibiting neuronal ferroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126430","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":"Apoptin-Derived Peptide Alleviates Temporal Lobe Epilepsy (TLE) by Limiting Neuronal Ca2+ Overload Through the HSPA1A–AP2B1 Axis","authors":"Zixiao Tan,&nbsp;Qilong Zhai,&nbsp;Jingwen Cui,&nbsp;Xiaoying Gao,&nbsp;Xingan Liu,&nbsp;Zhijie Fan,&nbsp;Yu Liu,&nbsp;Jiahang Sun","doi":"10.1002/cns.71193","DOIUrl":"10.1002/cns.71193","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To determine whether the apoptin-derived peptide (also named B9) reduces evoked seizure susceptibility and kainic acid (KA)-associated cognitive and molecular abnormalities, and to define whether these effects involve the heat shock protein family A member 1A (HSPA1A)–adaptor protein complex 2 subunit beta 1 (AP2B1) pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The therapeutic efficacy of B9 was examined in a pentylenetetrazol (PTZ)-induced acute seizure model and a KA-induced temporal lobe epilepsy (TLE) model. Electroencephalographic (EEG) recordings were performed to evaluate epileptiform activity. The Barnes maze test was used to assess cognitive function in epileptic mice. Western blotting, co-immunoprecipitation (Co-IP), immunofluorescence (IF), and calcium imaging were used to investigate the underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>B9 reduced seizure susceptibility, attenuated epileptiform activity, and improved spatial learning and memory. HSPA1A was markedly upregulated in TLE-related datasets and experimental models. B9 suppressed the expression of HSPA1A and disrupted its interaction with AP2B1, which restored O-linked β-N-acetylglucosamine (O-GlcNAc) modification and protein stability of AP2B1, preserved GluA2 expression, and limited neuronal Ca²⁺ overload. Knockdown of AP2B1 abolished the effects of B9 on evoked seizure susceptibility, cognitive performance, GluA2 abundance, and neuronal Ca²⁺ overload, whereas AP2B1 overexpression reproduced the reductions in PTZ-evoked seizure susceptibility and EEG activity observed with B9.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>B9 reduces PTZ-evoked seizure susceptibility and ameliorates KA-associated cognitive and molecular abnormalities through modulation of the HSPA1A–AP2B1 axis. These findings support B9 as a potential therapeutic strategy for TLE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101500","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":"Impacts of Cognitive Load and Task Initiation Timing on Gait Performance in Parkinson's Disease: A Dual-Task Paradigm Study","authors":"Shohei Okusa,&nbsp;Takehide Kimura,&nbsp;Kenya Tanamachi,&nbsp;Fuminari Kaneko,&nbsp;Yuka Yamada,&nbsp;Michiyuki Kawakami,&nbsp;Jin Nakahara,&nbsp;Morinobu Seki","doi":"10.1002/cns.71199","DOIUrl":"10.1002/cns.71199","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Gait impairment in Parkinson's disease (PD), especially under dual-task conditions, contributes to falls and reduced quality of life. Although the impact of cognitive load has been explored, the effect of the cognitive task's initiation timing relative to walking is unclear. We investigated how variations in cognitive load and the timing of task initiation affect gait performance in PD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twelve PD patients and 11 age-matched healthy controls (HCs) completed single-task walking and two arithmetic cognitive tasks (serial-5, serial-7). In dual-task trials, the cognitive task either preceded gait initiation (cognitive-first; C5, C7) or followed it (motor-first; M5, M7). Gait speed, cycle parameters, and inter-limb coordination were measured. Cognitive performance was primarily quantified as the answering speed. This exploratory study analyzed the dual-task data using linear mixed-effects models (LMM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In PD patients, gait speed was selectively reduced both by higher cognitive load and by initiating the cognitive task before walking (cognitive-first), whereas HCs showed no such effects. Inter-limb coordination of the lower limbs was reduced by higher cognitive load and, in PD patients, by the cognitive-first condition. The cognitive answering speed differed by task load but not by group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Gait in PD patients is particularly vulnerable when a high-load cognitive task is initiated before walking, suggesting that both the cognitive demand and the timing of task onset modulate dual-task interference. These findings may guide tailored dual-task assessments and rehabilitation strategies for PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101587","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":"Spinal Mechanisms of Testosterone Involved in Itch Regulation","authors":"Luying Chen,&nbsp;Xiaodong Wang,&nbsp;Lu Cheng,&nbsp;Pengtao Li,&nbsp;Zhenyu Wu,&nbsp;Hui Li","doi":"10.1002/cns.71196","DOIUrl":"10.1002/cns.71196","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background and Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Clinical and epidemiological data demonstrate that females exhibit higher itch sensitivity than males, and prior research has confirmed estrogen exacerbates pruritus to drive this sexual dimorphism. Nevertheless, it remains poorly defined whether testosterone, the primary androgen, exerts anti-pruritic effects and contributes to sex disparities in itch perception. This study therefore has three primary objectives: (1) to characterize testosterone's regulatory effects on acute and chronic itch across male and female mice; (2) to identify spinal androgen receptor-expressing neuronal populations mediating testosterone's anti-pruritic actions; (3) to elucidate the downstream GABAergic synaptic cascade by which testosterone suppresses spinal itch transmission.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;C57BL/6 mice and GRPR-GFP mice were used in this study. Behavioral tests were performed to evaluate the effects of exogenous testosterone administration, orchiectomy, androgen receptor (AR) antagonist flutamide, and GABA&lt;sub&gt;A&lt;/sub&gt; receptor (GABA&lt;sub&gt;A&lt;/sub&gt;R) antagonist bicuculline on acute itch induced by histamine or chloroquine and chronic itch induced by 2,4-dinitrofluorobenzene (DNFB), as well as anxiety-like behaviors assessed by elevated plus-maze (EPM) and open-field test (OFT). Double immunofluorescence staining was applied to detect the co-localization of AR and PAX2 in the spinal dorsal horn. Whole-cell patch-clamp electrophysiology was used to record synaptic transmission and excitability of GRPR&lt;sup&gt;+&lt;/sup&gt; neurons in spinal cord slices.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Testosterone contributed to sex differences in itch in mice. Exogenous testosterone suppressed histamine- or chloroquine-evoked acute itch and alleviated DNFB-induced chronic itch and anxiety-like behaviors. Orchiectomy enhanced itch sensitivity, which was reversed by testosterone replacement. AR was predominantly expressed on PAX2&lt;sup&gt;+&lt;/sup&gt; GABAergic inhibitory interneurons in the superficial spinal dorsal horn. Testosterone increased spontaneous inhibitory synaptic input and reduced excitability of GRPR&lt;sup&gt;+&lt;/sup&gt; neurons. The antipruritic effect of testosterone was blocked by intrathecal flutamide or bicuculline.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Testosterone inhibits itch transmission at the spinal level by activating AR on GABAergic interneurons, enhancing GABA release, and subsequently suppressing GRPR&lt;sup&gt;+&lt;/sup&gt; neurons via GABA&lt;sub&gt;A&lt;/sub&gt;R. Testosterone acts as an endogenous ant","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101681","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":"Eye-Tracking Phenotypes Across the Depressive Spectrum: Joint Modeling of Diagnostic Group and Symptom Severity","authors":"Xiangting Chen,&nbsp;Min Huang","doi":"10.1002/cns.71198","DOIUrl":"10.1002/cns.71198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To characterize eye-tracking alterations across the depressive spectrum and evaluate their value for diagnostic stratification and symptom severity estimation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, 183 participants completed a multi-paradigm eye-tracking battery. Group differences and associations with 17-item Hamilton Depression Rating Scale (HAMD-17) scores were examined with multiple-comparison correction and covariate adjustment. Classification, regression, and multi-task models used repeated nested resampling with fold-specific preprocessing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>False discovery rate (FDR)-significant between-group differences were observed for two first-fixation latency measures from lateral-gaze orienting and for antisaccade accuracy. Among 35 candidate features, 33 had covariate-adjusted group associations at <i>p</i> &lt; 0.05. Across 539 retained features, covariate-adjusted generalized additive models identified eight FDR-significant associations with HAMD-17. In multi-task analysis, Route B had numerically higher mean internal performance than Route A, although paired between-route differences were imprecisely estimated (accuracy, 0.929 vs. 0.864; macro F1, 0.928 vs. 0.859; R², 0.834 vs. 0.596). Regression-only performance was similar to Route B (R², 0.847).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Eye-tracking alterations spanned the depressive spectrum and were associated with symptom severity after covariate adjustment. Between-route differences were imprecisely estimated, and joint-task training showed no clear improvement in severity estimation. External and temporal validation are required before clinical use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101543","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":"Compound Ciwujia Granules Attenuate Stress-Induced Anxiety- and Depression-Like Behaviors via Inhibition of TNF-α-Associated Neuroinflammation in the dmPFC.","authors":"Fei Tian, Yi Li, Mengyu Dai, Yihan Guo, Bingbing Liao, Yingdan Zhang, Xin Gong, Lanying Liu, Dongdong Shi, Zhen Wang","doi":"10.1002/cns.71178","DOIUrl":"https://doi.org/10.1002/cns.71178","url":null,"abstract":"<p><strong>Aims: </strong>Compound Ciwujia Granules (CWJ) have shown antidepressant-like effects, but the neural and molecular mechanisms underlying these effects remain unclear. This study aimed to investigate the mechanisms by which CWJ ameliorates anxiety- and depression-like behaviors.</p><p><strong>Methods: </strong>A 6-week chronic unpredictable mild stress (CUMS) model was established in rats, and behavioral tests were performed to assess the antidepressant-like effects of CWJ. Resting-state functional magnetic resonance imaging (rs-fMRI), in vivo fiber photometry, and chemogenetic manipulation were used to identify the brain region and neuronal population involved in the effects of CWJ. Transcriptomic analysis combined with network pharmacology was used to predict candidate molecular pathways, which were further validated by quantitative real-time polymerase chain reaction, immunofluorescence, western blotting, and pharmacological interventions.</p><p><strong>Results: </strong>CWJ increased the open-arm ratio in the EPM, reduced FST immobility, and lowered serum corticosterone (CORT) levels in CUMS rats. Convergent rs-fMRI, c-Fos immunostaining, and fiber photometry identified that the dorsomedial prefrontal cortex (dmPFC) was a key brain region involved in the antidepressant-like effects of CWJ. CWJ increased glutamatergic neuronal activity and reduced neuroinflammatory responses associated with TNF-related inflammatory signaling in the dmPFC. Moreover, pharmacological activation of TNF-related inflammatory signaling partially attenuated the behavioral benefits of CWJ, supporting the involvement of  TNF-related inflammatory signaling in mediating its antidepressant effects.</p><p><strong>Conclusions: </strong>These findings suggest that CWJ attenuated CUMS-induced anxiety- and depression-like behaviors by restoring dmPFC glutamatergic neuronal activity and suppressing TNF-related neuroinflammation in the dmPFC.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71178"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101554","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}