CNS Neuroscience & Therapeutics最新文献

{"title":"Posture-Related Regional Homogeneity Abnormalities in Cerebral Small Vessel Disease: A Multi-Position MRI Study.","authors":"Yukun Zhang, Qi Dai, Weinv Fan, Hu Yu, Liang Hu, Shenyu Fan, Ling Ni, Danying Ma, Disen Wang, Wesley Surento, Xin Zhang, Rongfeng Qi, Jianjun Zheng, Bing Zhang","doi":"10.1002/cns.71140","DOIUrl":"10.1002/cns.71140","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebral small vessel disease (CSVD) is associated with altered spontaneous brain activity on resting-state functional magnetic resonance imaging (rs-fMRI). However, MRI studies usually overlook the potential effects of postural change. This study characterized posture-related alterations in spontaneous brain activity in CSVD patients.</p><p><strong>Materials and methods: </strong>Forty-one CSVD patients and 30 normal controls (NCs) underwent multi-position MRI, including upright and supine rs-fMRI. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated, and supine-upright differences (Δ) were derived. Mixed-design ANOVA assessed group, position, and interaction effects. Within-group and between-group differences were examined, followed by cognition-related analyses.</p><p><strong>Results: </strong>The main effect of posture on ReHo was observed in frontal, temporal, and parietal cortices and deep gray nuclei. In the upright position, CSVD patients had higher ReHo in the right anterior cingulate gyrus than NCs, which was associated with worse global cognitive function and a higher composite CSVD score. CSVD patients also exhibited widespread posture-related ReHo alterations. Regression analyses demonstrated that ΔReHo in the left hippocampus was positively associated with memory function, whereas ΔReHo in the right putamen and left calcarine cortex was associated with the composite CSVD score.</p><p><strong>Conclusion: </strong>Upright imaging and upright-supine comparison may help unmask latent posture-related ReHo abnormalities in patients with CSVD.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71140"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904881","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":"Neurobehavioral Association Between Macroscopic Network Decoupling and Reduced Eating Impulsivity: A Longitudinal fMRI Study in Bulimia Nervosa","authors":"Yulong Jia,&nbsp;Weihua Li,&nbsp;Demin Kong,&nbsp;Fengxia Yu,&nbsp;Guowei Wu,&nbsp;Yiling Wang,&nbsp;Jiani Wang,&nbsp;Zhenchang Wang,&nbsp;Lirong Tang,&nbsp;Peng Zhang","doi":"10.1002/cns.71129","DOIUrl":"10.1002/cns.71129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fluoxetine is an established pharmacological intervention for bulimia nervosa (BN); however, the macroscopic functional network remodeling underlying its efficacy in suppressing eating impulsivity remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fifty-eight patients with BN and 58 healthy controls assessed at both baseline and follow-up underwent resting-state functional magnetic resonance imaging (rs-fMRI). Network-Based Statistic (NBS) analysis with edgewise paired comparisons was used to identify whole-brain connectivity changes in patients with BN. The resulting BN-derived component was subsequently examined in both groups using a Group × Time analysis. Exploratory brain-behavior associations within BN were examined using Spearman and partial Spearman correlations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During follow-up, patients with BN showed significant improvements in depressive symptoms and externally driven eating behavior. Within-group NBS analysis identified a 23-edge component showing reduced functional connectivity in BN at follow-up, with network-level family-wise error correction (<i>p</i> &lt; 0.05). This component primarily involved dorsal attention, ventral attention/salience, and somatomotor networks. Whole-brain NBS analysis in healthy controls did not identify a significant longitudinal component. When mean connectivity of the BN-derived component was extracted in both groups, connectivity decreased more strongly in BN than in healthy controls (Group × Time <i>β</i> = −0.053, <i>p</i> = 0.027).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The follow-up period in patients with BN was accompanied by clinical improvement and reduced functional connectivity among attention-, salience-, and sensorimotor-related systems. These findings provide preliminary evidence of treatment-period-associated functional network reconfiguration in BN.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>ChiCTR2200066885</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862782","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":"GWAS of Tau-Neurodegeneration Mismatch Identifies New Risk Loci for Susceptibility to Tau","authors":"Fardin Nabizadeh,&nbsp;Hanieh Mohamadi,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative (ADNI)","doi":"10.1002/cns.71125","DOIUrl":"10.1002/cns.71125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In Alzheimer's disease (AD), neurodegeneration is primarily attributed to the accumulation of tau neurofibrillary tangles. However, the distribution patterns of both tau pathology and neurodegeneration vary across different brain regions and among individuals. Moreover, multiple factors may influence the relationship between tau burden and neurodegenerative processes. Identifying the genetic architecture associated with deviation in the tau-neurodegeneration relationship can provide deeper mechanistic insights and guide the development of precision medicine strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, I perform a genome-wide association study (GWAS) of cortical tau and thickness quantified by positron emission tomography (PET) and magnetic resonance imaging (MRI) in 794 participants from two cohorts of Alzheimer's disease Neuroimaging Initiative (ADNI) and A4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A GWAS was identified between the Tau/Neurodegeneration residual and two novel loci on chromosomes 7 and 14, with two SNPs (rs9323573 and rs9784993) exceeding the genome-wide significance threshold (<i>p</i> ≤ 5 × 10⁻⁸). SNP rs9323573 is located in STXBP6 on chromosome 14, while rs9784993 is in AKAP9 on chromosome 7, both of which were directly genotyped. The minor allele G of both SNPs (rs9323573, MAF = 0.221, <i>p</i> = 2.60 × 10⁻⁸; rs9784993, MAF = 0.197, <i>p</i> = 4.92 × 10⁻⁸) was associated with lower Tau/Neurodegeneration residuals, indicating higher-than-expected neurodegeneration given tau levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GWAS of tau-related neurodegeneration identified two novel genetic variants in the loci AKAP9 and STXBP6 leading to higher than expected regional neurodegeneration given the tau level. Identifying genetic factors involved in tau-neurodegeneration mismatch may improve our understanding regarding the potential mechanistic downstream leading to susceptibility or resilience to tau pathology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862832","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":"Focal Cortical Dysplasia Type II: Somatic Mutations, Molecular Mechanisms, and Integrative Multi-Omics Framework.","authors":"Zesheng Li, Yihe Wang, Jianwei Shi, Yumin Luo, Yongzhi Shan, Guoguang Zhao","doi":"10.1002/cns.71170","DOIUrl":"10.1002/cns.71170","url":null,"abstract":"<p><strong>Background: </strong>Focal cortical dysplasia Type II (FCD II) is a major cause of drug-resistant epilepsy in children. Somatic mosaic variants affecting the PI3K-AKT-mTOR pathway are implicated in a substantial proportion of cases. The links between genotype, cellular pathology, epileptogenic networks, and clinical outcome remain incompletely defined.</p><p><strong>Methods: </strong>This review synthesizes evidence on somatic mTOR-pathway variants, lesion development, pathological cell populations, circuit mechanisms, single-cell and spatial multi-omics approaches in FCD II.</p><p><strong>Results: </strong>The developmental timing, lineage distribution, and local expansion of somatic variants influence lesion extent and phenotypic heterogeneity. Dysmorphic neurons may contribute to epileptogenicity through altered intrinsic excitability and synaptic function, whereas balloon cells may predominantly affect local circuits through secretory and microenvironmental mechanisms. mTOR hyperactivation may also alter interneuron development, subtype specification, and synaptic connectivity, thereby disrupting excitation-inhibition balance. Single-cell and spatial approaches, including RNA velocity, pseudotime analysis, chromatin-age inference, and somatic genotyping, provide tools to resolve pathological cell states and lineage trajectories.</p><p><strong>Conclusions: </strong>FCD II should be considered a mosaic developmental disorder involving both cell-autonomous and non-cell-autonomous mechanisms. Integrating somatic variant detection with cellular, spatial, electrophysiological, and surgical outcomes from matched patient tissue may enable biologically meaningful stratification and support the development of novel therapies.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71170"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023373","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":"Developmental Deficiency of Oligodendrocytes and Myelination in the Central Nervous System of the Fetal Alcohol Syndrome Mouse Model.","authors":"Xiaoling Liang, Rulan Yi, Zhidan Ke, Yi Zhang, Liang Zhou","doi":"10.1002/cns.71157","DOIUrl":"10.1002/cns.71157","url":null,"abstract":"<p><strong>Background: </strong>Fetal alcohol spectrum disorder (FASD) is a severe condition characterized by physical and neurodevelopmental abnormalities in the fetus resulting from prenatal alcohol exposure (PAE) or prenatal and lactation alcohol exposure (PLAE). Behavioral abnormalities associated with white matter damage have been extensively investigated in FASD patients and animal models, which suggested the involvement of myelination in FASD pathology. However, the impact of FASD on oligodendrocytes (OLs) and myelination within the central nervous system (CNS) and the underlying mechanisms are little discovered. This study aimed to reveal the effect and role of PLAE on CNS myelination in a FASD mouse model.</p><p><strong>Methods: </strong>We set up a PLAE approach to generate the FASD mouse model to explore the effects of FASD on CNS myelination. Open-field test, elevated plus maze, and tail suspension test were used to evaluate possible behavior deficiency of the FASD mice. Myelination in the cortex and hippocampus of the FASD mice was detected at postnatal days 14, 21, and 90 (P14, P21, and P 90). Then we counted the number of oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs) to reveal the cell fates of oligodendrocyte lineage cells in the FASD mice. Next, we set up BLBP+/GFAP+ double-staining to monitor the possible dysfunction of radial glial cells, which may contribute to the myelination deficiency in FASD mice. Finally, an FDA-approved pro-myelination drug, clemastine fumarate (CF), was used to validate the possible advantages of myelin restoration and behavior defects in the FASD mice.</p><p><strong>Results: </strong>Impaired myelination was observed in the cortex and hippocampus of the male FASD offspring, associated with hyperactivity-like behaviors, whereas the female FASD mice exhibited delayed myelin formation and normal behaviors, indicating a gender-specific manner of FASD pathology. Furthermore, the different myelination deficiency between male and female FASD mice is due to the fact that only the male FASD mice exhibited a failure of oligodendrocyte differentiation. Additionally, FASD exerts an impact on the quantity and differentiation of radial glia cells, which may contribute to the myelination defect. Finally, CF-treated male FASD mice showed myelin regeneration, leading to partial alleviation of behavioral abnormality in the male FASD mice.</p><p><strong>Conclusion: </strong>Our data reveal a gender-related deficiency of CNS myelination in the FASD mouse model, suggesting a potential therapy target for FASD.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71157"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954499","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":"Advances in Targeting Central Cholinergic Dysfunction for Neurodegenerative Diseases: From Pharmacotherapy to Neuromodulation.","authors":"Lei Lei, Xiaoyu Hu, Ruida Lu, Jian-Jun Yang, Qingsheng Meng","doi":"10.1002/cns.71151","DOIUrl":"10.1002/cns.71151","url":null,"abstract":"<p><strong>Background: </strong>The central cholinergic system has long been a cornerstone therapeutic target for neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). For decades, acetylcholinesterase inhibitors (AChEIs) have served as the standard symptomatic treatment, providing cognitive and functional relief by enhancing synaptic acetylcholine levels. However, their limited efficacy and inability to modify disease progression underscore the fundamental constraint of purely neurochemical enhancement, especially in the context of progressive cholinergic neuron loss.</p><p><strong>Results and conclusion: </strong>This review critically examines the evolution of cholinergic therapies beyond AChEIs. We first explore the shift from broad neurotransmitter enhancement toward precision targeting of receptor subtypes and the development of multi-target pharmacological strategies. Furthermore, we highlight how neuromodulation techniques-including vagus nerve stimulation, deep brain stimulation, and non-invasive brain stimulation-directly engage and restore dysfunctional neural circuits, moving beyond mere chemical enhancement. Emerging directions such as advanced cholinergic imaging, gene therapy, and cell-based regeneration are also discussed as promising pathways toward true disease modification. Ultimately, the integration of sophisticated pharmacological agents with circuit-level neuromodulation represents the next frontier in treating cholinergic dysfunction across the spectrum of neurodegenerative disorders, advancing the therapeutic goal from chemical enhancement to circuit repair and regeneration.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71151"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928506","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":"Oligodendrocyte-Targeted SGK1.1 Inhibition Alleviates White Matter Injury and Cognitive Impairment in Alzheimer's Disease via Modulation of HDAC2 Phosphorylation.","authors":"Shiji Deng, Shenghan Gao, Chao Zhou, Zhen Lan, Huiya Li, Jiang Chen, Yuhao Xu, Jiashuo Li, Pinyi Liu, Siyuan Zhang, Xinyu Bao, Tingting Wang, Yun Xu, Xiaolei Zhu","doi":"10.1002/cns.71150","DOIUrl":"10.1002/cns.71150","url":null,"abstract":"<p><strong>Background: </strong>White matter (WM) abnormalities contribute to cognitive decline in Alzheimer's disease (AD). However, the mechanisms underlying AD-associated WM vulnerability remain incompletely understood, and effective therapeutic strategies to improve WM pathology are still limited.</p><p><strong>Methods: </strong>Sgk1.1-specific RNAscope combined with Olig2 immunostaining was used to assess the cellular distribution of Sgk1.1 transcripts. Oligodendrocyte-targeted adeno-associated virus (AAV)-mediated Sgk1.1 knockdown was performed in 5 × FAD mice. Sgk1.1 overexpression was conducted in primary oligodendrocyte precursor cells (OPCs) in vitro. Phosphoproteomic profiling, co-immunoprecipitation, Phos-tag Western blot, and phospho-site mutagenesis were used to identify downstream mechanisms. A bilateral common carotid artery stenosis (BCAS) model was employed to assess broader relevance.</p><p><strong>Results: </strong>Sgk1.1 mRNA was predominantly elevated in oligodendrocyte-lineage cells of 5 × FAD mice prior to overt myelin loss. Targeted knockdown of oligodendroglial Sgk1.1 ameliorated cognitive deficits, preserved myelin ultrastructure, and promoted oligodendrocyte maturation. Conversely, Sgk1.1 overexpression arrested OPC differentiation and suppressed myelin gene expression in vitro. Mechanistically, SGK1.1 promoted HDAC2 phosphorylation at S422/S424, and blocking this phosphorylation partially reversed SGK1.1-induced maturation deficits. Furthermore, oligodendrocyte-targeted Sgk1.1 overexpression exacerbated WM injury and cognitive impairment in the BCAS model.</p><p><strong>Conclusion: </strong>Our findings identify oligodendrocyte-targeted SGK1.1 inhibition as a tractable therapeutic strategy to preserve WM integrity and cognitive function, and define HDAC2 S422/S424 phosphorylation as a mechanistic node linking SGK1.1 signaling to impaired myelination in AD and related demyelinating disorders.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71150"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910366","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":"Development and Initial Validation of the Japanese Version of the Movie for the Assessment of Social Cognition in Adults With Autism Spectrum Disorder","authors":"Muneaki Ogata,&nbsp;Hikaru Hori,&nbsp;Asuka Katsuki,&nbsp;Hitoshi Iida,&nbsp;Leo Gotoh,&nbsp;Haruka Fujino","doi":"10.1002/cns.71131","DOIUrl":"10.1002/cns.71131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to develop a Japanese version of the Movie for the Assessment of Social Cognition (MASC-J) and to conduct a preliminary evaluation of its reliability and validity in adults with autism spectrum disorder (ASD) compared with healthy controls (HCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty adults with ASD and 30 HCs completed the MASC-J, Reading the Mind in the Eyes Test (RMET), Autism-Spectrum Quotient, and Japanese Adult Reading Test. Internal consistency, test–retest reliability, partial convergent validity with the RMET, and discriminative ability using receiver operating characteristic analysis were examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MASC-J scores were significantly lower in the ASD group than in the HC group. The MASC-J showed acceptable discriminative ability (area under the curve = 0.804), acceptable internal consistency, and excellent test–retest reliability. In the total sample, MASC-J scores correlated with RMET scores, but this association was not significant within either group. In the ASD group, MASC-J scores were positively associated with estimated full-scale IQ. Overmentalizing and absence-of-mentalizing errors were more frequent in the ASD group, whereas undermentalizing errors did not differ between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings provide preliminary support for the MASC-J as a measure of social cognition in Japanese-speaking adults with ASD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862808","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":"Integrated Genomic and Proteomic Analysis Reveals T-B Lymphocyte Signatures in the MYCN Driven “Immune Desert” of Specific Neuroblastoma Subtypes","authors":"Jia-Jian Hu,&nbsp;Wen-Juan Kang,&nbsp;Jia-Tong Hu,&nbsp;Ye-Xiong Li,&nbsp;Feng-Ju Song,&nbsp;Min Deng","doi":"10.1002/cns.71054","DOIUrl":"10.1002/cns.71054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aims to systematically dissect how MYCN amplification shapes the immunosuppressive tumor microenvironment (TME) in high-risk neuroblastoma, elucidating key mechanisms underlying immune evasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed an integrated multi-omics analysis of bulk RNA-seq (<i>n</i> = 721), single-cell RNA-seq (<i>n</i> = 9), proteomic data (<i>n</i> = 49) and spatial transcriptomics (Visium, with external validation in melanoma). Analyses included unsupervised clustering, cell–cell communication inference, transcriptional regulatory network reconstruction, and spatial proximity assessment to map the immune landscape.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A distinct molecular subtype (Class C), defined by MYCN amplification and poor prognosis, exhibited a comprehensive “immune desert” phenotype characterized by low immune scores and minimal leukocyte infiltration. Single-cell analysis confirmed significant depletion of T and B lymphocytes within the Class C TME. Dysregulated transcriptional networks were identified, including upregulation of REL and EOMES in T cells—with EOMES potentially driving exhaustion via regulation of Transient Receptor Potential (TRP) genes, and REL inhibition enhancing cytotoxic function in vitro. A unique immunosuppressive B-cell subset (B7) engaged in enhanced crosstalk with exhausted T cells and harbored a MYC-centered network linked to cell cycle dysregulation and poor survival. Spatial transcriptomics revealed significant proximity between B7-active regions and Treg/exhaustion-enriched areas, externally validated in melanoma. Proteomic data validated elevated REL expression in MYCN-amplified tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work delineates the immunosuppressive architecture of MYCN-driven neuroblastoma, revealing novel regulatory nodes within specific lymphocyte compartments. Integrating single-cell, spatial, and proteomic evidence, we propose REL inhibition as a therapeutic candidate, the EOMES/TRP axis as a bioinformatically supported hypothesis, and the B7/MYC hub as a hypothesis supported by transcriptomic and spatial evidence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862813","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":"Crosstalk Between Cortical Plasticity and Peripheral Nervous Injury: Insights, Mechanisms, and Future Directions","authors":"Cong Cheng,&nbsp;Dong Gao,&nbsp;Yaojie Shen,&nbsp;Xi Wang,&nbsp;Junxi Dai,&nbsp;Yaoxian Xiang,&nbsp;Zongyuan Jiang,&nbsp;Zongqi You,&nbsp;Junjian Jiang","doi":"10.1002/cns.71090","DOIUrl":"10.1002/cns.71090","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Cortical plasticity is essential for functional recovery after peripheral nervous injury (PNI). Different injury types, from compressive to metabolic neuropathies, lead to distinct patterns of cortical reorganization, calling for a better understanding of the mechanisms and treatment options for each injury type.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review summarizes current evidence from preclinical, neuroimaging, electrophysiological, and clinical studies on the link between cortical plasticity and PNI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The review describes the key molecular pathways that shape adaptive and maladaptive cortical reorganization across injury types, examines the value of neuroimaging and blood-based biomarkers for tracking plasticity, and evaluates the current evidence for drug and rehabilitation treatments. Major gaps remain, including the limited testing of biomarkers across different injury types, the lack of PNI-specific clinical trials, and the difficulty of applying laboratory findings to personalized treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Moving forward, progress depends on validating biomarkers for each injury type, conducting well-designed trials in PNI patients, and combining drug, rehabilitation, and whole-body treatment approaches. This review offers a practical guide for turning mechanistic knowledge into clinical focus in PNI-related cortical plasticity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872295","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}