CNS Neuroscience & Therapeutics最新文献

{"title":"Association of Left Ventricular Function With Cerebral Small Vessel Disease in a Community-Based Population","authors":"Yingying Yang,&nbsp;Xueli Cai,&nbsp;Mengyuan Zhou,&nbsp;Yiyi Chen,&nbsp;Jingtao Pi,&nbsp;Mengxi Zhao,&nbsp;Yulu Shi,&nbsp;Jing Jing,&nbsp;Weiqi Chen,&nbsp;Hongyi Yan,&nbsp;Xia Meng,&nbsp;Yongjun Wang,&nbsp;Yuesong Pan,&nbsp;Yilong Wang","doi":"10.1111/cns.70226","DOIUrl":"https://doi.org/10.1111/cns.70226","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objectives</h3>\u0000 \u0000 <p>The relationship of cardiac function with cerebral small vessel disease (CSVD) remains unknown. The study aimed to investigate the association between left ventricular (LV) function and CSVD in a community-based population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Community-dwelling residents in China from the cross sectional survey of the PRECISE (PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events) cohort were included. LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were measured for LV systolic function, and mitral E/A ratio (the ratio of the peak trans-mitral filling velocity during early diastole and late diastole) was evaluated for LV diastolic function by transthoracic echocardiogram (TTE). Total CSVD score and CSVD imaging makers including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), and enlarged perivascular spaces (EPVS) were assessed. The associations of cardiac function with CSVD were analyzed using ordinal or binary logistic regression models. Restricted cubic spline models fitted for logistic regression models were used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 3063 participants with available TTE and brain MRI data were included in the study. In the multivariable logistic regression analysis, LVEF and LVFS were not associated with total CSVD score or markers of CSVD. E/A ratio showed a negative correlation with total CSVD score (cOR, 0.89, 95% CI: 0.80–0.98, <i>p</i> = 0.01). Participants with E/A ≤ 0.8 or ≥ 2 had a higher total CSVD score than those with 0.8 &lt; E/A &lt; 2 (cOR 1.20, 95% CI: 1.00–1.43, <i>p</i> = 0.046). E/A ratio was also correlated with lacunes, moderate to severe EPVS, and periventricular WMH. Logistic regression analyses with restricted cubic spline further demonstrated that a lower E/A ratio were associated with a higher total CSVD score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study showed that mitral E/A ratio was associated with nonhemorrhagic CSVD. LV diastolic dysfunction assessed by TTE provides clues for the early warning of high CSVD burden.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447122","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":"Clinical Features of Glutamic Acid Decarboxylase-65 Neurological Autoimmunity: A Case Series From China","authors":"Zhandong Qiu,&nbsp;Fang Xu,&nbsp;Mengyao Zhang,&nbsp;Xixi Yang,&nbsp;Yan Han,&nbsp;Dawei Li,&nbsp;Liang Liu,&nbsp;Jia Chen,&nbsp;Lehong Gao,&nbsp;Qing Xue,&nbsp;Yue Hou,&nbsp;Ying Sun,&nbsp;Li Di,&nbsp;Chunqiu Fan,&nbsp;Junhua Liang,&nbsp;Yue Han,&nbsp;Huiqing Dong,&nbsp;Junwei Hao,&nbsp;Zheng Liu","doi":"10.1111/cns.70237","DOIUrl":"https://doi.org/10.1111/cns.70237","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To explore the clinical phenotypes, characteristics, immunotherapy response, and outcomes of glutamic acid decarboxylase-65 (GAD65) neurological autoimmunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective review of patients diagnosed with GAD65 neurological autoimmunity in the Department of Neurology at Xuanwu Hospital over the past 6 years (2017–2023). The clinical and laboratory data, imaging, therapeutic response, and long-term prognosis of those patients were collected and analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 37 patients displaying significant neurological impairment, there were 14 males (37.8%) and 23 females (62.2%), with a median age of onset of 41.5 (25–59) years and a median interval of 9 (1.5–36) months from onset to a definitive diagnosis. Clinical phenotypes included epilepsy (15, 40.5%), limbic encephalitis (7, 18.9%), brainstem dysfunction (2, 5.4%), parkinsonism (2, 5.4%), peripheral neuropathy (3, 8.1%), cerebellar ataxia (1, 2.7%), and overlap syndromes (7, 18.9%). Out of 36 patients who received immunotherapy, the median time from onset to initiation of immunotherapy was 8.5 (1.5–37.5) months. Four cases were lost to follow-up, leaving a median follow-up period of 20.5 (16–37.25) months among the remaining 32 patients. Most patients (26, 81.3%) responded positively to immunotherapy, with some showing mild improvement or no response. Some patients showed inadequate responses to treatments such as mycophenolate mofetil (MMF), but significant improvement is observed after switching to rituximab (RTX). The relationship between the timing of initiating immunotherapy and prognosis by Spearman's rank correlation only showed weak correlation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The clinical spectrum of GAD65 neurological autoimmunity appeared highly diverse. Immunotherapy can benefit the majority of patients, and early treatment appeared to be associated with good prognosis. RTX may be more effective than MMF; however, this requires more rigorous prospective studies to explore.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447123","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":"Ntoco Promotes Ferroptosis via Hnrnpab-Mediated NF-κB/Lcn2 Axis Following Traumatic Brain Injury in Mice","authors":"Qiang Wang,&nbsp;Hanjun Zuo,&nbsp;Huaqin Sun,&nbsp;Xiao Xiao,&nbsp;Zhao Wang,&nbsp;Tingyu Li,&nbsp;Xiaolei Luo,&nbsp;Yanyun Wang,&nbsp;Tao Wang,&nbsp;Juanjuan Li,&nbsp;Linbo Gao","doi":"10.1111/cns.70282","DOIUrl":"https://doi.org/10.1111/cns.70282","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Emerging evidence highlights the involvement of long non-coding RNAs (lncRNAs) and ferroptosis in the pathogenesis of traumatic brain injury (TBI). However, the regulatory role of lncRNAs in TBI-induced ferroptosis remains poorly understood. This study aims to investigate the role of a specific lncRNA, noncoding transcript of chemokine (C-C motif) ligand 4 (<i>Ccl4</i>) overlapping (<i>Ntoco</i>), in the regulation of ferroptosis following TBI and explore its potential as a therapeutic target.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The expression levels of <i>Ntoco</i> following controlled cortical injury (CCI) in mice were measured using real-time PCR. Behavioral tests post-injury were assessed using the rotarod test and Morris water maze, and lesion volume was evaluated using micro-MRI. <i>Ntoco</i> binding proteins were identified using RNA pull-down and RNA immunoprecipitation. RNA sequencing was employed to identify <i>Ntoco</i>-related pathways. Western blotting and co-immunoprecipitation were used to measure protein levels and ubiquitination processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Ntoco</i> upregulation was observed in CCI mice. <i>Ntoco</i> knockdown inhibited neuron ferroptosis, reduced lesion volume, and improved spatial memory following TBI. <i>Ntoco</i> overexpression promoted ferroptosis in neurons. Mechanistically, <i>Ntoco</i> facilitated K48-linked ubiquitination and degradation of proteins by binding to Hnrnpab, suppressing the NF-κB/Lcn2 signaling pathway. This included reduced phosphorylation of IkBα, increased phosphorylation of IKKα/β, nuclear translocation of the NF-κB p65 subunit, and elevated Lcn2 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that <i>Ntoco</i> plays a crucial role in TBI-induced ferroptosis by modulating the NF-κB/Lcn2 signaling pathway. Targeting <i>Ntoco</i> may provide a promising therapeutic strategy to mitigate ferroptosis and improve outcomes following TBI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447121","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":"NONHSAT141192.2 Facilitates the Stemness and Radioresistance of Glioma Stem Cells via the Regulation of PIK3R3 and SOX2","authors":"Sihan Wang,&nbsp;Haolang Ming,&nbsp;Zhen Wang,&nbsp;Xingye Zhai,&nbsp;Xinyue Zhang,&nbsp;Di Wu,&nbsp;Yin Bo,&nbsp;Hang Wang,&nbsp;Yuanbo Luo,&nbsp;Zhenfeng Han,&nbsp;Lingyu Hao,&nbsp;Yijia Xiang,&nbsp;Xu Han,&nbsp;Zengguang Wang,&nbsp;Yi Wang","doi":"10.1111/cns.70279","DOIUrl":"https://doi.org/10.1111/cns.70279","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioma stem cells (GSCs) contribute to the initiation, recurrence, metastasis, and drug resistance of glioblastoma multiforme (GBM). Long noncoding RNAs (lncRNAs) are critical modulators in the development and progression of GBM; however, specific lncRNAs related to GSCs remain largely unexplored. This study aims to identify dysregulated lncRNAs in GSCs, unravel their contributions to GBM progression, and propose new targets for diagnosis and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GeneChip analysis was utilized to identify lncRNAs in GSCs. The expression of RNAs was examined using quantitative real-time PCR. Cell Counting Kit-8, tmorsphere formation assay, limiting dilution assay, apoptosis detection and intracranial xenograft models were performed to assess the stemness and radioresistance of GSCs. Transcriptomics analysis, RNA immunoprecipitation and dual-luciferase experiments were conducted for mechanistic studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NONHSAT141192.2 exhibited elevated expression levels in aggressive GBM tissues compared to lower-grade gliomas. Silencing NONHSAT141192.2 resulted in a considerable decrease in GSC proliferation, tumor sphere formation, self-renewal and the expression of key stem cell markers. Furthermore, depletion of NONHSAT141192.2 enhanced GSC sensitivity to radiation, indicated by diminished viability and tumorsphere formation, increased cell apoptosis, and decreased tumor growth in intracranial xenograft models. Mechanistically, NONHSAT141192.2 upregulates the expression of SOX2 and PIK3R3 by sponging miR-4279, influencing GSC characteristics and their resistance to radiation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study highlights a significant relationship between NONHSAT141192.2, GSC stemness, and radioresistance, emphasizing its potential as a therapeutic target for GBM treatment and radiosensitization.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70279","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438978","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":"Hydrogen Sulfide Alleviates Schizophrenia-Like Behavior Through Regulating Apoptosis by S-Sulfhydrylation Modification","authors":"Xinzhe Du,&nbsp;Wei Hu,&nbsp;Meiqi Liu,&nbsp;Jinzhi Lv,&nbsp;Yao Gao,&nbsp;Xiao Wang,&nbsp;Wentao Zhao,&nbsp;Junxia Li,&nbsp;Xinrong Li,&nbsp;Xiaohua Cao,&nbsp;Zhifen Liu,&nbsp;Yong Xu,&nbsp;Sha Liu","doi":"10.1111/cns.70278","DOIUrl":"https://doi.org/10.1111/cns.70278","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>We initiated an exploration of the relationship between hydrogen sulfide (H₂S) and Schizophrenia (SZ) as well as its mechanism at the three levels of population study, cellular investigation, and animal model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Clinical data and peripheral blood samples from 78 patients with SZ and 83 healthy controls (HC) were collected for the detection of H₂S levels (ChiCTR (Chinese Clinical Trial Registry) 900026776). MK801 (Dizocilpine) was used to establish SZ models in cells and rats, with sodium hydrosulfide (NaHS) serving as an exogenous H₂S donor. H₂S levels in plasma and hippocampal tissue of rats were measured using Enzyme Linked Immunosorbent Assay (ELISA). Terminal dUTP Nick End Labeling (TUNEL) staining was employed to detect apoptosis, enzyme activity was determined to assess apoptotic protease activity, neuron damage was identified by Nissl staining, and the protein S-sulfhydrylation test was utilized to evaluate alterations in apoptosis-associated protein S-sulfhydrylation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>H₂S content significantly decreased in the plasma of SZ patients and in the plasma and hippocampal tissue of SZ model rats. NaHS pretreatment reduced MK801-induced apoptosis in SH-SY5Y cells. SZ model rats exhibited increased behavioral abnormalities, hippocampal apoptosis, and reduced S-sulfhydrylation of an apoptosis-related protein, both restored after NaHS pretreatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>H₂S content is significantly reduced in SZ, and supplementation of H₂S can alleviate SZ-like behavior by inducing S-sulfhydration of apoptotic proteins.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431402","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":"Neural Oscillations in the Somatosensory and Motor Cortex Distinguish Dexmedetomidine-Induced Anesthesia and Sleep in Rats","authors":"Dengyun Ge,&nbsp;Chuanliang Han,&nbsp;Chang Liu,&nbsp;Zhiqiang Meng","doi":"10.1111/cns.70262","DOIUrl":"https://doi.org/10.1111/cns.70262","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anesthesia is featured by behavioral and physiological characteristics such as decreased sensory and motor function, loss of consciousness, etc. Some anesthetics such as dexmedetomidine (DEX), induce electroencephalogram signatures close to non-rapid eye movement sleep. Studies have shown that sleep is primarily driven by the activation of subcortical sleep-promoting neural pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>However, the neuronal level electrophysiology features of anesthesia and how they differ from sleep is still not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In the present study, we recorded neuronal activity simultaneously from somatosensory cortex (S1) and motor cortex (M1) during awake, sleep, and DEX-induced anesthesia in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results show that DEX increased local field potential (LFP) power across a relatively wide band (1–25 Hz) in both S1 and M1. The coherence between S1 LFP and M1 LFP increased significantly in the delta and alpha bands. Power spectrum analysis during DEX-induced anesthesia revealed relatively high power in the delta and alpha bands, but low power in the theta and beta bands. Overall, the firing rate of individual neurons decreased after DEX. Correlation analysis of firing rate and LFP power indicate that more neurons were correlated, either positively or negatively, with LFPs during DEX-induced anesthesia compared to sleep.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>Although these results showed enhancement of cortical LFP power in both DEX-induced anesthesia and sleep, different patterns of spike-field correlation suggest that the two states may be regulated by different cortical mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Distinguishing anesthesia from sleep with neural oscillations could lead to more personalized, safer, and more effective approaches to managing consciousness in medical settings, with the potential for broad applications in neuroscience and clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431751","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":"Relationships Between Glymphatic System Activity and Tau Burden, Dopaminergic Impairment, Abnormal Glucose Metabolism in Progressive Supranuclear Palsy","authors":"Fangyang Jiao,&nbsp;Qingmin Wang,&nbsp;Jiayi Zhong,&nbsp;Huamei Lin,&nbsp;Jiaying Lu,&nbsp;Luyao Wang,&nbsp;Min Wang,&nbsp;Fengtao Liu,&nbsp;Jiehui Jiang,&nbsp;Chuantao Zuo","doi":"10.1111/cns.70284","DOIUrl":"https://doi.org/10.1111/cns.70284","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Progressive supranuclear palsy (PSP) is a primary tauopathy characterized by dopaminergic impairment and abnormal glucose metabolism. The glymphatic system can promote the elimination of tau protein. The association between glymphatic function and pathological hallmark in neuroimaging remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Diffusion tensor imaging (DTI) and positron emission tomography (PET) scanning with ¹⁸F-Florzolotau, ¹⁸F-FPCIT, and ¹⁸F-FDG were performed in PSP patients. DTI analysis along the perivascular space (ALPS) index was computed to assess glymphatic function, while the semi-quantitative value was employed to measure tau burden and dopaminergic impairment. The PSP-related pattern (PSPRP) served as an indicator of abnormal metabolic brain network activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PSP patients exhibited changes in ALPS index and tau deposition. ALPS index, tau deposition, and PSPRP expression showed significant correlations with clinical scores. Additionally, ALPS index was correlated with tau deposition and PSPRP expression. However, neither ALPS index nor the clinical scores were correlated with striatum dysfunction. Finally, tau deposition in subcortical regions and PSPRP expression exhibited mediating effects between ALPS index and clinical scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The glymphatic dysfunction is associated with tau deposition and abnormal metabolic brain network activity and is independent of dopaminergic impairment in PSP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431752","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":"NFAT1 Signaling Contributes to Bone Cancer Pain by Regulating IL-18 Expression in Spinal Microglia","authors":"Xuetai Chen,&nbsp;Ying Zeng,&nbsp;Zizhu Wang,&nbsp;Jixiang Zhu,&nbsp;Fengyun Liu,&nbsp;Mingxuan Zhu,&nbsp;Jiayi Zheng,&nbsp;Qingdaiyao Chen,&nbsp;Dongxu Zhai,&nbsp;Yangyang Chen,&nbsp;Jiayao Niu,&nbsp;Zhouya Xue,&nbsp;Guan Sun,&nbsp;Feng Li,&nbsp;Zhiqiang Pan","doi":"10.1111/cns.70222","DOIUrl":"https://doi.org/10.1111/cns.70222","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to test the hypothesis that nuclear factor of activated T cells 1 (NFAT1) signaling contributes to bone cancer pain by regulating interleukin (IL)-18 expression in spinal microglia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was performed on male mice using a Lewis lung carcinoma-induced bone cancer pain model. Nociceptive behaviors were evaluated by measuring mechanical allodynia, thermal hyperalgesia, and spontaneous pain. Expression levels were measured via real-time quantitative polymerase chain reaction, western blotting, and immunofluorescence analysis. The effect of pharmacologic intervention of spinal NFAT1/IL-18 signaling on bone cancer pain was the primary outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NFAT1 expression was upregulated in the spinal microglia after tumor inoculation. Pharmacological inhibition of NFAT1 upregulation prevented and reversed bone cancer-related pain behaviors. In spinal microglia, NFAT1 inhibition decreased p38 MAPK phosphorylation and IL-18 production. Blocking NFAT1 signaling suppressed tumor-induced neuronal sensitization and microglial activation as well as activation of the N-methyl-D-aspartate receptor and the subsequent Ca²⁺-dependent signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Microglia NFAT1-p38 signaling contributes to bone cancer pain through IL-18-mediated central sensitization in spinal microglia. NFAT1 could be a potential target for therapeutic intervention to prevent bone cancer pain.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70222","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423914","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":"Astaxanthin Inhibits Ferroptosis of Hippocampal Neurons in Kainic Acid-Induced Epileptic Mice by Activating the Nrf2/GPX4 Signaling Pathway","authors":"Shihao Chen,&nbsp;Linqian Zhao,&nbsp;Xing Jin,&nbsp;Qichang Liu,&nbsp;Yuqing Xiao,&nbsp;Huiqin Xu","doi":"10.1111/cns.70238","DOIUrl":"https://doi.org/10.1111/cns.70238","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Epilepsy, a prevalent neurological disorder, is distinguished by episodic abnormal discharges of neurons within the brain, resulting in transient brain dysfunction. Prior research has identified a novel form of cell death termed ferroptosis, which is intricately linked to the initiation and progression of epilepsy. It has been demonstrated that astaxanthin (AST) can inhibit ferroptosis by enhancing the activity of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby providing cytoprotection. Therefore, this study aims to investigate whether AST can alleviate neuronal ferroptosis in epilepsy by activating the Nrf2/GPX4 pathway, thereby exerting a neuroprotective effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>By constructing a kainic acid (KA)-induced epilepsy mouse model and a KA-induced HT22 cell model, we employed behavioral testing, Western blot analysis, quantitative real-time reverse transcription qRT-PCR, ferroptosis-related assay kits, immunofluorescence staining, and other methods. These methodologies were utilized to investigate the protective effects and underlying mechanisms of AST on ferroptosis in KA-induced epileptic mice and HT22 neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results demonstrate that AST pretreatment alleviates KA-induced epileptic behaviors and cognitive impairments in mice and mitigates ferroptosis indicators such as lipid peroxidation and mitochondrial morphological alterations. This neuroprotective effect appears to be mediated by the activation of the Nrf2/GPX4 signaling axis. In vitro studies further revealed that AST confers neuroprotection against KA-induced HT22 neuronal cell death, an effect that is abrogated by an Nrf2 inhibitor. Hence, the neuroprotective properties of AST are significantly associated with the modulation of the Nrf2-mediated ferroptosis pathway, as corroborated by bioinformatics analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AST effectively inhibits neuronal ferroptosis in both in vivo and in vitro epilepsy models via the Nrf2/GPX4 pathway. This finding suggests that AST holds promise as a potential therapeutic agent for the treatment of epilepsy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424092","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":"Effects of Pretreatment With Coenzyme Q10 (CoQ10) and High-Intensity Interval Training (HIIT) on FNDC5, Irisin, and BDNF Levels, and Amyloid-Beta (Aβ) Plaque Formation in the Hippocampus of Aβ-Induced Alzheimer's Disease Rats","authors":"Samira Puoyan-Majd,&nbsp;Abdolhossein Parnow,&nbsp;Masome Rashno,&nbsp;Rashid Heidarimoghadam,&nbsp;Alireza komaki","doi":"10.1111/cns.70221","DOIUrl":"https://doi.org/10.1111/cns.70221","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Physical exercise has been shown to protect against cognitive decline in Alzheimer's disease (AD), likely through the upregulation of brain-derived neurotrophic factor (BDNF). Recent studies have reported that exercise activates the FNDC5/irisin pathway in the hippocampus of mice, triggering a neuroprotective gene program that includes BDNF. This study aimed to investigate the effects of 8 weeks of pretreatment with coenzyme Q10 (CoQ10) and high-intensity interval training (HIIT), both individually and in combination, on FNDC5, irisin, BDNF, and amyloid-beta (Aβ) plaque formation in the hippocampus of Aβ-related AD rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, 72 male Wistar rats were randomly assigned to one of the following groups: control, sham, HIIT (low intensity: 3 min running at 50%–60% VO2max; high intensity: 4 min running at 85%–90% VO2max), Q10 (50 mg/kg, orally administered), Q10 + HIIT, AD, AD + HIIT, AD + Q10, and AD + Q10 + HIIT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aβ injection resulted in a trend toward decreased levels of FNDC5, irisin, and BDNF, alongside increased Aβ plaque formation in the hippocampus of Aβ-induced AD rats. However, pretreatment with CoQ10, HIIT, or their combination significantly restored hippocampal levels of FNDC5, irisin, and BDNF, while also inhibiting Aβ plaque accumulation in these rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Pretreatment with CoQ10 and HIIT improved the Aβ-induced reduction in BDNF levels probably through the FNDC5/irisin pathway and preventing Aβ plaque formation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 2","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424108","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}