CNS Neuroscience & Therapeutics最新文献

{"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}

{"title":"Integrative Transcriptomics and Machine Learning Identify Temporal Stress Signatures and Astrocytic Neurocan Associated With Hypothalamic Injury.","authors":"Weihao Zhu, Chenyu Li, Mengting He, Rui Shi, Xia Liu, Weibo Shi, Bin Cong","doi":"10.1002/cns.71219","DOIUrl":"https://doi.org/10.1002/cns.71219","url":null,"abstract":"<p><strong>Background: </strong>Stress-related neurological dysfunction evolves dynamically, but molecular markers distinguishing stress stages remain limited. We aimed to characterize temporal hypothalamic transcriptomic changes and identify molecular signatures for stress-stage discrimination.</p><p><strong>Methods: </strong>Whole-transcriptome sequencing was performed in mouse hypothalami after stress. Differential expression, temporal clustering, co-expression network analysis, and machine learning were integrated to identify stress-associated mRNA and miRNA signatures. Candidate markers were validated by RT-qPCR and single-nucleus RNA sequencing. Ncan function was further evaluated by protein supplementation, perineuronal net analysis, behavioral testing, and regulatory network analysis.</p><p><strong>Results: </strong>mRNAs exhibited strong temporal sensitivity and captured stage-specific transcriptional remodeling, whereas miRNAs primarily reflected stress regardless of duration. A six-mRNA signature (Ncan, Mt2, Nab2, Ptch1, and Catspere1/Catspere2) accurately distinguished control, acute stress, and chronic stress (accuracy, 1.000), while an 11-miRNA signature robustly classified stress states (accuracy, 0.944). Both signatures were validated by RT-qPCR and nested cross-validation, with accuracies of 0.898 and 0.890, respectively. Ncan was consistently top-ranked, predominantly expressed in astrocytes, progressively downregulated by stress, and its supplementation restored PNNs and alleviated depressive-like behaviors. Virtual Ncan knockout disrupted the stress network, with Ctcf predicted as its upstream regulator.</p><p><strong>Conclusion: </strong>Our study identifies distinct stress-stage and stress-state transcriptomic signatures and highlights astrocytic Ncan as a candidate biomarker that may contribute to stress-induced neural injury by regulating PNN homeostasis.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259893","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":"Efficacy and Safety of Multidisciplinary Sandwich Regimen in AQP4-IgG+ NMOSD With Preconception B-Cell Depletion During Perigravidity.","authors":"Li Xiao, Gengxin Lu, Qian Gao, Feiyan Wan, Zhenze Lu, Wei Qiu, Chengfang Xu, Yaxin Lu, Lejia Xu, Tingting Xia, Jiajing Chao, Yu Fu, Zhuanggui Chen, Rui Li, Yanyu Chang, Yuge Wang, Bing Qin, Yaqing Shu","doi":"10.1002/cns.71222","DOIUrl":"https://doi.org/10.1002/cns.71222","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Neuromyelitis optica spectrum disorder (NMOSD) predominantly affects women of childbearing age, accompanied by markedly elevated relapse risks during pregnancy and postpartum periods, bringing great challenges to perigravid management. At present, there is no standardized gestational therapeutic regimen for NMOSD worldwide, and data on perigravid application of B-cell depleting agents including rituximab and inebilizumab remain limited. For patients exposed to B-cell depleting agents before conception, balancing disease control and fetal safety is an urgent clinical problem to be solved.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This multicenter prospective cohort study aimed to evaluate the efficacy and safety of a three-stage multidisciplinary \"sandwich\" management regimen in AQP4-IgG-positive pregnant women with NMOSD exposed to B-cell depleting agents before conception. Maternal disease activity, pregnancy outcomes, neonatal conditions, and offspring growth and developmental characteristics within the first year of life were analyzed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 8 AQP4-IgG-positive pregnant women with NMOSD who received B-cell depleting agents within 9 months prior to conception were enrolled from multiple centers between January 2022 and October 2024, including 3 patients treated with inebilizumab and 5 patients treated with rituximab. All subjects received a unified three-stage intervention: B-cell depleting agents were discontinued upon confirmed pregnancy; low-dose azathioprine combined with low-dose glucocorticoids was administered during gestation; B-cell depleting agents were reinitiated at 2 weeks postpartum. Multidisciplinary teams consisting of neurology, obstetrics, clinical pharmacy, and neonatology departments conducted full-cycle monitoring and follow-up. Primary observation indicators included maternal relapse events, Expanded Disability Status Scale (EDSS) scores, B-cell counts, gestational complications, gestational age at delivery, neonatal physical indicators, Apgar scores, congenital malformations, as well as offspring growth and neurodevelopment and vaccination safety from birth to 1 year of age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;All subjects achieved term live births without severe obstetric complications. Seven patients remained relapse-free throughout pregnancy and postpartum period with stable or improved EDSS scores; one patient discontinued all medications during gestation and suffered a relapse at 1 month postpartum. Neonatal physical indicators and Apgar scores were generally normal, one neonate presented mild hypospadias and two developed transient neonatal abnormalities; neonatal B-cell counts at birth and 1 month of age were within normal ranges. One-year follow-up showed normal physical and neurodevelopment in all offspring with safe vaccination procedures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;For AQP4-IgG-positive pregnant women with NMOSD exposed to B-cell depleting agents","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149259940","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":"METTL3 Increases Temozolomide Resistance in MGMT-Negative Glioblastoma by Enhancing CBX5 mRNA Stability in an m6A-IGF2BP2-Dependent Manner","authors":"Hui Deng,&nbsp;Ruoyu Chen,&nbsp;Daohong Qu,&nbsp;Cifu Qu,&nbsp;Jia Shi","doi":"10.1002/cns.71164","DOIUrl":"10.1002/cns.71164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We examined whether chromobox protein 5 (CBX5) contributes to temozolomide (TMZ) resistance in O⁶-methylguanine-DNA methyltransferase (MGMT)-negative glioblastoma (GBM) and whether it is regulated by methyltransferase-like 3 (METTL3)-dependent N⁶-methyladenosine (m⁶A) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Public datasets, clinical specimens, MGMT-negative cells, and subcutaneous xenografts were examined using functional, mechanistic, and rescue assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the CGGA693 cohort of the Chinese Glioma Genome Atlas, higher CBX5 expression remained associated with shorter survival after multivariable adjustment (hazard ratio 1.178, 95% confidence interval 1.050–1.322; <i>p</i> = 0.005). CBX5 depletion increased TMZ sensitivity, apoptosis, and DNA damage, reduced ATM phosphorylation and RAD51 abundance, and restricted TMZ-treated xenograft growth; overexpression produced reciprocal effects in vitro. METTL3 depletion reduced CBX5 expression, mRNA stability, m⁶A enrichment, and wild-type reporter activity but did not significantly affect the m⁶A motif-mutant reporter. IGF2BP2 depletion reduced CBX5 protein and mRNA stability, whereas RNA immunoprecipitation supported an IGF2BP2–CBX5 mRNA association. CBX5 re-expression partially reversed METTL3 depletion-induced effects on viability and DNA damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>METTL3-dependent m⁶A modification and IGF2BP2-associated stabilization help maintain CBX5 expression, contributing to TMZ resistance and ATM–RAD51-associated signaling in MGMT-negative GBM models.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101585","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":"Connectivity-Guided Individualized iTBS of the Posterior Parietal Cortex in Enduring Anorexia Nervosa: Network-Level Target Engagement and Multimodal Response in a Single Case.","authors":"Enrico Collantoni, Sofia Gentili, Arianna Menardi, Antonino Vallesi, Giovanni Librizzi, Elena Tenconi, Andrea Serino, Gaia Risso, Daniele Olivo, Fabio Sambataro, Angela Favaro, Valentina Meregalli","doi":"10.1002/cns.71206","DOIUrl":"https://doi.org/10.1002/cns.71206","url":null,"abstract":"<p><strong>Aims: </strong>Anorexia nervosa (AN) is a severe, often enduring disorder with scarce biological treatments, largely unable to address its core implicit features: habit-like food restriction and body-experience disturbances. We report a single-case application of resting-state connectivity-guided intermittent theta-burst stimulation (iTBS) to the posterior parietal cortex (PPC), a hub for body representation, peripersonal space, and affordance-based action.</p><p><strong>Methods: </strong>A 31-year-old woman with 12 years of treatment-resistant restricting AN, enrolled in an ongoing sham-controlled feasibility trial, underwent 20 active iTBS sessions to an individualized left-PPC site maximally coupled with a body-representation × affordance reference network, assessed at baseline, post-treatment, and four-month follow-up.</p><p><strong>Results: </strong>The protocol was fully feasible and well tolerated, without significant adverse events. Clinical change was gradual, with most of the weight gain occurring after the stimulation period: BMI rose from 15.65 to 16.01 at four-month follow-up and 16.40 over subsequent clinical follow-up. Blinded global improvement was minimal; anxiety fell below threshold, whereas eating-disorder and body-shape scores remained at floor. Target-reference connectivity increased in the a priori direction, toward the healthy-control mean. Exploratory measures changed heterogeneously, only partly tracking engagement.</p><p><strong>Conclusion: </strong>This case supports the feasibility and mechanistic plausibility of individualized parietal targeting in enduring AN, motivating a controlled trial to test its efficacy.</p><p><strong>Trial registration: </strong>The parent trial is registered on ClinicalTrials.gov (NCT07106645).</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71206"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163338","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}