CNS Neuroscience & Therapeutics最新文献

{"title":"Analysis of Two Neuroanatomical Subtypes of Parkinson's Disease and Their Motor Progression Based on Semi-Supervised Machine Learning","authors":"Hao Zhou,&nbsp;Yuqing Wu,&nbsp;Shuoying Chen,&nbsp;Yi Xing,&nbsp;Jingru Ren,&nbsp;Weiguo Liu","doi":"10.1111/cns.70277","DOIUrl":"https://doi.org/10.1111/cns.70277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The high heterogeneity of Parkinson's disease (PD) hinders personalized interventions. Brain structure reflects damage and neuroplasticity and is one of the biological bases of symptomatology. Subtyping PD in the framework of brain structure helps in the prediction of disease trajectories and optimizes treatment strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included a total of 283 <i>de novo</i> PD and 141 healthy controls (HC). Structural heterogeneity between PD and HC was compared, and patients were classified using Heterogeneity through Discriminative Analysis. Gray matter volume (GMV), clinical symptoms, and substantia nigra free water (SNFW) among all subtypes were compared. These subtypes were followed for an average of 2.5 years to monitor motor impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Early PD patients possessed higher GMV heterogeneity than HC, and two subtypes based on GMV patterns were identified. Subtype 1 showed widespread GMV reductions, while subtype 2 had an increased volume in the basal ganglia and parts of the cortex. Subtype 1 had more severe motor and non-motor symptoms, as well as higher posterior SNFW. The whole-brain GMV in the PD group was negatively correlated with posterior SNFW; basal ganglia volume in subtype 1 was negatively correlated with Unified Parkinson's Disease Rating Scale (UPDRS)-III scores, whereas no linear correlation was found in subtype 2. The UPDRS-III progression rate was higher in subtype 1 than in subtype 2 (2.52 vs 0.92 points/year).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The heterogeneity of PD patients reflected the changes in their brain structure. The identification of these changes helps the classification of patients into different subtypes, additionally supported by clinical manifestations and SNFW, with consequent benefits for clinical consultancy and precision medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423821","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":"H2S Donor SPRC Ameliorates Ischemic Stroke by Upregulating CD24","authors":"Chenye Wang,&nbsp;Sha Li,&nbsp;Qixiu Li,&nbsp;Haiyan Xi,&nbsp;Jiejia Li,&nbsp;Qing Zhu,&nbsp;Pinwen Wu,&nbsp;Yi-Zhun Zhu,&nbsp;Yicheng Mao","doi":"10.1111/cns.70243","DOIUrl":"https://doi.org/10.1111/cns.70243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ischemic stroke is well-known for its high mortality and morbidity, but its treatment remains to be explored due to the current limitations. For example, severe neuroinflammation occurs after ischemic stroke; however, effective neuroinflammatory inhibitors are still lacking. Thus, the development of new therapeutic targets of inhibiting neuroinflammation is urgent. CD24 is a small heavy glycosylated protein, which plays a critical role in neural development and acts as an inflammatory suppressor in tumors and autoimmune diseases. But the role of CD24 in ischemic stroke remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The role of CD24 in ischemic stroke should be explored. Additionally, the potential relationship between the H₂S donor, S-propargyl-cysteine (SPRC) and CD24 in ischemic stroke should be revealed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mechanism studies have been performed both in vitro and in vivo to verify the CD24-mediated inflammation and migration. SPRC has been applied to treat ischemic stroke, and its potential association with CD24 has been studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The overexpression of CD24 can inhibit the nuclear factor kappa B (NF-κB) inflammatory signaling pathway and promote the migration ability of M2 microglia cells via Src/Fak/Pyk2 signaling pathway in an inflammatory model of BV2 cells. SPRC can upregulate the level of endogenous H₂S via cystathionase-β-synthase (CBS) and it indirectly plays a role in upregulating CD24.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CD24 could be a potential target of inhibiting neuroinflammation. SPRC reduces inflammation in ischemic stroke by regulating the CD24/Iκ-Bα/NF-κB inflammatory signaling pathway and improves the migration ability of M2 microglia via CD24/Src/Fak/Pyk2 signaling pathway, which further alleviates the inflammatory response at the lesion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423822","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":"Fronto-Parietal and Language Network Connectivity and Its Association With Gene Expression Profiles in Bipolar Disorder Before and After Treatment","authors":"Leyi Zhang,&nbsp;Haohao Yan,&nbsp;Chunguo Zhang,&nbsp;Xiaoling Li,&nbsp;Jiaquan Liang,&nbsp;Chaohua Tang,&nbsp;Weibin Wu,&nbsp;Wen Deng,&nbsp;Guojun Xie,&nbsp;Wenbin Guo","doi":"10.1111/cns.70236","DOIUrl":"https://doi.org/10.1111/cns.70236","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The resting-state functional connectivity (FC) patterns of the fronto-parietal network (FPN) and language network (LN) underlying bipolar disorder (BD) are obscure. This study aimed to uncover abnormal FC patterns of FPN and LN underlying BD and their evolution following treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Imaging data at rest state and clinical variables were acquired from 82 patients with BD (with 43 finishing the follow-up) and 88 healthy controls (HCs). Seed-based FC analysis was performed, and correlations between FCs and clinical variables were investigated with whole-brain multiple regression analyses. Furthermore, a neuroimaging–transcription spatial association analysis was conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, BD patients presented elevated FPN-LN and FPN–prefrontal gyrus FCs, and hyperconnectivity between the LN and bilateral thalamus, right angular gyrus (AG), and right cerebellum. Following 3 months of treatment intervention, there were decreased FCs between the FPN and left superior temporal gyrus (STG), left superior frontal gyrus (SFG), left insula, and bilateral middle temporal gyrus (MTG) (part of LN). Neuroimaging transcription analysis discovered genes correlated with FC alterations in BD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Aberrant FC patterns of FPN and LN might be involved in the neural pathogenetic and therapeutic mechanisms of BD. We also provided potential genetic pathways underlying these functional impairments in BD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424059","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":"Integration of Methylation and Gene Expression Deciphered Candidate Biomarkers DAB2IP and SMYD3 in Delayed Encephalopathy After Carbon Monoxide Poisoning","authors":"Hongyi Yan,&nbsp;Ding Yuan,&nbsp;Yan Zhang,&nbsp;Haihua Luo,&nbsp;Pinpin Jiang,&nbsp;Yapeng Zhang,&nbsp;Yue Wu,&nbsp;Linlin Hou,&nbsp;Yue Cheng,&nbsp;Fang Yang,&nbsp;Yuqi Du,&nbsp;Huanzhou Zhu,&nbsp;Linshuang Zhao,&nbsp;Yi Li,&nbsp;Yong Jiang,&nbsp;Yanxia Gao","doi":"10.1111/cns.70270","DOIUrl":"https://doi.org/10.1111/cns.70270","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The objective of this study is to explore the regulatory role of DNA methylation in delayed encephalopathy after carbon monoxide poisoning (DEACMP) and to identify candidate epigenetic biomarkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, multi-omics analyses such as methylomics, transcriptomics, pyrophosphate sequencing, qRT-PCR, immunohistochemistry, and western blotting were utilized to investigate the role of epigenetic regulation and altered gene expression in the pathogenesis of DEACMP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using integrated analysis, we identified 168 differentially methylated CpGs sites, 334 differentially expressed genes, and two differentially methylated and differentially expressed genes (DAB2IP and SMYD3) in the DEACMP group. The pyrosequencing results further revealed hypomethylation of DAB2IP and hypermethylation of SMYD3. Moreover, we verified the upregulation of DAB2IP expression accompanied by the downregulation of SMYD3 expression in the DEACMP rats model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study, based on dysregulated DNA methylation and gene expression profiles, identified and validated two DEACMP-related genes (DAB2IP and SMYD3) that could serve as epigenetic biomarkers and potential therapeutic targets for DEACMP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423823","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":"Emergency Admission Plasma D-Dimer and Prothrombin Activity: Novel Predictors for Clinical Outcomes After Thrombectomy in Acute Ischemic Stroke With Large Artery Occlusion","authors":"Shandong Jiang,&nbsp;Peizheng Guo,&nbsp;Linxin Cai,&nbsp;Cong Qian,&nbsp;Jun Yu,&nbsp;Liang Xu,&nbsp;Xu Li,&nbsp;Xianyi Chen,&nbsp;Fang Bing,&nbsp;Yuan Yuan,&nbsp;Zhongju Tan,&nbsp;Jing Xu,&nbsp;Jianru Li","doi":"10.1111/cns.70267","DOIUrl":"https://doi.org/10.1111/cns.70267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The coagulation system is intrinsically linked to pathological mechanisms and progression of ischemic stroke. However, the role of preoperative coagulation function in determining the functional outcomes of acute ischemic stroke patients following large artery occlusion (AIS-LVO) has not been extensively evaluated in peer-reviewed literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We utilized logistic regression analyses, complemented by the construction of receiver operating characteristic (ROC) curves, to identify significant predictive factors for poor prognosis following endovascular thrombectomy (EVT). Additionally, subgroup analyses were conducted to further assess the prognostic efficacy of coagulation function across different subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 607 patients were enrolled, with 335 (55.19%) experiencing an unfavorable outcome. Multivariate regression analysis identified preoperative D-dimer and PTA as independent predictors of 3-month prognosis. After adjusting for confounders, elevated preoperative D-dimer levels (≥ 715 mg/L), identified by cut-off value, were a significant predictor of poor prognosis, with 2.51-fold higher risk compared to the normal range. Conversely, elevated PTA levels (≥ 85.5%) were significantly and inversely associated with poor prognosis, indicating a reduced risk of 0.39 times. Furthermore, the combination of elevated D-dimer and reduced PTA demonstrated a synergistic effect, markedly increasing the risk of poor outcomes in AIS-LVO patients. Subgroup analyses revealed that failed recanalization, comorbid diabetes, and non–middle cerebral artery (MCA) occlusion significantly influence the predictive value of D-dimer and PTA for clinical outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elevated admission D-dimer and reduced PTA levels are independent predictors of poor prognosis in patients with AIS-LVO, and there is a synergistic interaction between the two variables.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397133","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":"Examining the Impact of Microglia on Ischemic Stroke With an Emphasis on the Metabolism of Immune Cells","authors":"Jing Lv,&nbsp;Yang Jiao,&nbsp;Xinya Zhao,&nbsp;Xin Kong,&nbsp;Yanwei Chen,&nbsp;Lu Li,&nbsp;Xuyang Chen,&nbsp;Xufeng Tao,&nbsp;Deshi Dong","doi":"10.1111/cns.70229","DOIUrl":"https://doi.org/10.1111/cns.70229","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ischemic stroke, a major cause of disability and the second leading cause of death, poses a significant public health challenge. Post-stroke inflammation can harm the blood–brain barrier and worsen neurological deficits, which are key factors in neuronal damage in patients with ischemic stroke. Microglia are crucial in the central nervous system, involved in inflammation, neuronal damage, and repair after cerebral ischemia. While cellular immune metabolism has been widely studied, its role in ischamic stroke remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This review aims to examine how inflammation affects the phenotypic characteristics of immune cells after ischemic stroke and to explore the effects of the immune metabolic microenvironment on the phenotypic profiles and functions of microglia in ischemic stroke.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The review refers to the available literature in PubMed, searching for critical terms related to Ischemic stroke, neuroinflammation, microglia, and immunometabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>In this review, we found that during stroke progression, microglia can dynamically switch between pro-inflammatory and anti-inflammatory phenotypes. Microglial glycometabolism includes oxidative phosphorylation and glycolysis, and lipid metabolism involves lipid synthesis and breakdown. Modulating the production of inflammatory mediator precursors can induce an anti-inflammatory phenotype in microglia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, studying microglial metabolic pathways and their products may offer new insights for ischemic stroke treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397132","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":"H4K12 Lactylation Activated-Spp1 in Reprogrammed Microglia Improves Functional Recovery After Spinal Cord Injury","authors":"Xiaokun Wang,&nbsp;Geliang Zhou,&nbsp;Junjun Xiong,&nbsp;Wu Ye,&nbsp;Yu Gao,&nbsp;Haofan Wang,&nbsp;Dishui Pan,&nbsp;Yongjun Luo,&nbsp;Zheng Zhou","doi":"10.1111/cns.70232","DOIUrl":"https://doi.org/10.1111/cns.70232","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) is a severe condition leading to significant disability and high mortality. The role of the secreted phosphoprotein 1 (SPP1) signaling pathway in SCI, which is quickly activated after injury, is critical for intercellular communication but remains poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to explore the function and regulatory mechanisms of the SPP1 signaling pathway in SCI and investigate its potential as a therapeutic target for improving functional recovery after injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing (scRNA-seq) was employed to identify ligands and receptors of the SPP1 signaling pathway, particularly in microglia/macrophages. Recombinant SPP1 (rSPP1) was used in vitro and in vivo to assess its effects on neuronal maturation, mitochondrial energy in axons, and functional recovery after SCI. Pseudotime analysis was conducted to examine the role of <i>Spp1</i> in microglial activation and proliferation. DNA-pulldown and in vitro experiments were performed to investigate the upstream regulatory proteins of <i>Spp1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The SPP1 signaling pathway is primarily localized in microglia after SCI, with rSPP1 promoting neuronal maturation and enhancing mitochondrial function in axons. Injection of rSPP1 into the injured spinal cord resulted in significant improvement in functional recovery. Pseudotime analysis indicated that <i>Spp1</i> is involved in the activation and proliferation of microglia. Histone H4 lysine 12 lactylation (H4K12la) was found to promote the transcription of <i>Spp1</i> in reprogrammed microglia postinjury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Our findings reveal a novel regulatory mechanism involving <i>Spp1</i> in SCI, particularly its role in microglial activation, mitochondrial function, and glycolytic reprogramming. This new insight provides a deeper understanding of its contribution to the injury response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study uncovers a previously unreported mechanism of <i>Spp1</i> in SCI, offering a potential therapeutic target for SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397172","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":"Age-Specific Functional Connectivity Changes After Partial Sleep Deprivation Are Correlated With Neurocognitive and Molecular Signatures","authors":"Liyong Yu,&nbsp;Xuanyi Chen,&nbsp;Yuqi He,&nbsp;Xiaojuan Hong,&nbsp;Siyi Yu","doi":"10.1111/cns.70272","DOIUrl":"https://doi.org/10.1111/cns.70272","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study aimed to investigate age-specific alterations in functional connectivity after sleep deprivation (SD) and decode brain functional changes from neurocognitive and transcriptomic perspectives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we examined changes in global and regional graph measures, particularly regional network strength (RNS), in 41 young participants and 36 older participants with normal sleep and after 3 h of SD. Additionally, by utilizing cognitive probabilistic maps from Neurosynth and gene expression data from the Allen Human Brain Atlas, we applied partial least-squares regression analysis to identify the neurocognitive and transcriptional correlates of these RNS changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After SD, older participants exhibited decreased RNS in the default mode network (DMN) and dorsal attention network, with increased RNS in the visual network. Young participants also showed decreased RNS in the DMN, notably in the left inferior parietal lobe, left dorsolateral prefrontal cortex, and left posterior cingulate cortex. In young participants, SD-induced RNS changes significantly correlated with cognitive processes such as “attention,” “cognitive control,” and “working memory,” while in older participants, they correlated with “learning,” “focus,” and “decision.” Gene-category enrichment analysis indicated that specific genes related to signal transduction, ion channels, and immune signaling might influence SD pathophysiology by affecting functional connectivity in young participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study elucidates shared and age-specific brain functional network alterations associated with SD, providing a neurocognitive and molecular basis for understanding the underlying pathophysiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70272","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380623","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":"Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia","authors":"Yiqiang Zhi,&nbsp;Yan Shi,&nbsp;Danping Lu,&nbsp;Dan Xu","doi":"10.1111/cns.70260","DOIUrl":"https://doi.org/10.1111/cns.70260","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary spastic paraplegia (HSP) is a group of rare genetic neurodegenerative disorders characterized by corticospinal tract abnormalities. But frequently, abnormalities of proteins implicated in HSP have been identified in brain disorders of childhood, raising the possibility that early brain developmental mechanism underlying HSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>Here we summarized the clinical features of 89 HSP subtypes and found most have onset of symptoms earliest reported in infancy or early childhood. Importantly, HSP patients showed early brain developmental related phenotypes such as microcephaly, ventricular enlargement, and corpus callosum dysplasia. In addition, the expression trajectories analysis showed HSP genes were diffusely expressed across all human prenatal cortical regions and most genes enriched from post-conception weeks 8–24, periods characterized by neuro progenitor proliferation and neurogenesis. Furthermore, studies utilizing patient derived induced pluripotent stem cells (iPSCs)/organoids and mouse models have suggested that most HSP proteins play either direct or indirect roles in the development of the central nervous system. Therefore, HSP possesses a neurodevelopmental aspect and is not merely a degenerative disease, which may aid in better understanding the pathogenesis of this disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380829","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":"Discovery of Novel Pain Regulators Through Integration of Cross-Species High-Throughput Data","authors":"Ying Chen,&nbsp;Akhilesh K. Bajpai,&nbsp;Nan Li,&nbsp;Jiahui Xiang,&nbsp;Angelina Wang,&nbsp;Qingqing Gu,&nbsp;Junpu Ruan,&nbsp;Ran Zhang,&nbsp;Gang Chen,&nbsp;Lu Lu","doi":"10.1111/cns.70255","DOIUrl":"https://doi.org/10.1111/cns.70255","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Chronic pain is an impeding condition that affects day-to-day life and poses a substantial economic burden, surpassing many other health conditions. This study employs a cross-species integrated approach to uncover novel pain mediators/regulators.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used weighted gene coexpression network analysis to identify pain-enriched gene module. Functional analysis and protein-protein interaction (PPI) network analysis of the module genes were conducted. RNA sequencing compared pain model and control mice. PheWAS was performed to link genes to pain-related GWAS traits. Finally, candidates were prioritized based on node degree, differential expression, GWAS associations, and phenotype correlations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A gene module significantly over-enriched with the pain reference set was identified (referred to as “pain module”). Analysis revealed 141 pain module genes interacting with 46 pain reference genes in the PPI network, which included 88 differentially expressed genes. PheWAS analysis linked 53 of these genes to pain-related GWAS traits. Expression correlation analysis identified Vdac1, Add2, Syt2, and Syt4 as significantly correlated with pain phenotypes across eight brain regions. NCAM1, VAMP2, SYT2, ADD2, and KCND3 were identified as top pain response/regulator genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The identified genes and molecular mechanisms may enhance understanding of pain pathways and contribute to better drug target identification.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380373","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}