CNS Neuroscience & Therapeutics最新文献

{"title":"LncRNA ENSSSCG00000035331 Alleviates Hippocampal Neuronal Ferroptosis and Brain Injury Following Porcine Cardiopulmonary Resuscitation by Regulating the miR-let7a/GPX4 Axis","authors":"Mao Zhang,&nbsp;Wenbin Zhang,&nbsp;Ziwei Chen,&nbsp;Lu He,&nbsp;Qijiang Chen,&nbsp;Pin Lan,&nbsp;Lulu Li,&nbsp;Xianlong Wu,&nbsp;Xingui Wu,&nbsp;Jiefeng Xu","doi":"10.1111/cns.70377","DOIUrl":"https://doi.org/10.1111/cns.70377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following successful cardiopulmonary resuscitation, those survivors of cardiac arrest (CA) often suffer from severe brain injury, and the latter can result in significant mortality and morbidity. Emerging evidence implicates that ferroptosis is involved in the pathogenesis of post-resuscitation brain injury, and its regulatory mechanisms remain to be investigated. Recently, some studies manifested that long noncoding RNAs could be critical regulators of cell ferroptosis in diverse ischemia–reperfusion injuries of vital organs. This study was designed to explore the role and mechanism of a newly screened long noncoding RNA ENSSSCG00000035331 in alleviating post-resuscitation hippocampal neuronal ferroptosis and further investigate its potential regulation by a novel antioxidant sulforaphane.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Healthy male pigs and mice were used to establish the models of CA and resuscitation in vivo. A hypoxia/reoxygenation (H/R) model using primary porcine hippocampal neurons was constructed to replicate post-resuscitation brain injury in vitro. We found that the expression of ENSSSCG00000035331 was significantly decreased in the post-resuscitation impaired hippocampus using RNA sequencing analysis and verification. Subsequently, ENSSSCG00000035331 overexpression significantly reduced ferroptosis-related ferrous iron and reactive oxygen species production while markedly increased glutathione and further alleviated post-resuscitation brain injury. Mechanistically, ENSSSCG00000035331 interacted with miR-let7a, then inhibited its binding with glutathione peroxidase 4 (GPX4) mRNA and finally promoted the recovery of the latter's translation after H/R stimulation. In addition, sulforaphane treatment significantly increased ENSSSCG00000035331 and GPX4 expression while markedly decreased miR-let7a expression and hippocampal neuronal ferroptosis and finally alleviated post-resuscitation brain injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlighted that ENSSSCG00000035331 was a critical regulator of hippocampal neuronal ferroptosis after CA and resuscitation by targeting the miR-let7a/GPX4 axis, and additionally, sulforaphane might be a promising therapeutic agent for alleviating post-resuscitation brain injury by regulating the signaling axis mentioned above.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836282","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":"MK5 Regulates Microglial Activation and Neuroinflammation in Experimental Stroke Models","authors":"Xingzhi Wang,&nbsp;Wenqi Mao,&nbsp;Li Du,&nbsp;Fei Wang,&nbsp;Ye Pang,&nbsp;Yangdanyu Li,&nbsp;Guangci Xu,&nbsp;Guiyun Cui","doi":"10.1111/cns.70395","DOIUrl":"https://doi.org/10.1111/cns.70395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Microglial activation plays a crucial role in neuroinflammation following ischemic stroke. This study was conducted to investigate the role and potential mechanisms of MK5 within microglial cells in the inflammatory response following ischemic stroke in mice in vivo and in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Microglia-specific conditional MK5 knockout (MK5 cKO) mice and their control mice (MK5^f/f) were subjected to middle cerebral artery occlusion (MCAO). BV2 cells (a mouse microglial cell line) were transfected with small interfering RNA (siRNA) to knock down MK5 levels and subsequently exposed to oxygen–glucose deprivation/reperfusion (OGD/R) to simulate ischemic conditions in vitro. Following MCAO, behavioral tests and infarct volume measurements were conducted. Levels of cytokines and microglial markers were evaluated using qPCR and Western blotting, while immunofluorescence was employed to observe microglial activation. Additionally, Western blotting was performed to assess the phosphorylation of HSP27 and NF-κB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the control group, the knockout of the MK5 gene in microglia significantly exacerbated neurological deficits and increased infarct volume in MCAO mice. The loss of the MK5 promoted inflammation by upregulating pro-inflammatory factors and downregulating anti-inflammatory factors, while also enhancing microglial activation in both MCAO mice and BV2 microglial cells subjected to OGD/R. Furthermore, the knockout of the MK5 gene in microglia reduced the phosphorylation levels of HSP27 and increased the phosphorylation levels of NF-κB in the aforementioned models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Microglial MK5 plays a critical role in the ischemic neuroinflammatory response by regulating the phosphorylation of HSP27 and NF-κB, positioning it as a potential target for stroke treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836283","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":"Prediction and SHAP Analysis Integrating Morphological and Hemodynamic Parameters for Unruptured Intracranial Aneurysm Occlusion After Flow Diverter Treatment","authors":"Hongchen Zhang,&nbsp;Chuanhao Lu,&nbsp;Zhen Hu,&nbsp;Deyu Sun,&nbsp;Liang Li,&nbsp;Hongxing Wu,&nbsp;Hua Lu,&nbsp;Bin Lv,&nbsp;Jun Wang,&nbsp;Shuhui Dai,&nbsp;Xia Li","doi":"10.1111/cns.70386","DOIUrl":"https://doi.org/10.1111/cns.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although most unruptured intracranial aneurysms (UIAs) have good prognosis after flow diverter (FD) treatment, some remain unoccluded for extended periods, posing a persistent rupture risk. This study aims to develop a predictive model for UIA occlusion after FD treatment through integrating morphological and hemodynamic parameters, which may be critical for personalized postoperative management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from patients with single UIAs treated with stand-alone FD were collected from June 2018 to December 2022 in four cerebrovascular disease centers. Morphological parameters were obtained from 3D reconstructed aneurysm models, and hemodynamic parameters were derived by computational fluid dynamics (CFD) analysis. A predictive model for aneurysm occlusion was constructed using various machine learning algorithms, including logistic regression, Random Forest, XGBoost, and K-Nearest Neighbors. Model performances were evaluated through repeated cross-validation, 0.632 bootstrap, and 0.632+ bootstrap. Shapley additive explanation (SHAP) analysis was employed to assess the contribution of each parameter to UIA occlusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventy-nine patients were reviewed; a total of 51 cases met the criteria, with an average age of 53.9 ± 9.9 years. The average aneurysm diameter was 3.72 ± 2.72 mm, comprising 29 occlusions and 22 non-occlusions. Five variables were selected for further modeling, including follow-up time &gt; 6 months, aneurysm rupture ratio (ArR), occlusion ratio (OsR), parent artery wall shear stress (WSS), and the change of parent artery WSS. Logistic regression outperformed other algorithms, achieving an area under the curve (AUC) above 0.75, indicating good predictive performance. SHAP analysis revealed that the change of parent artery WSS contributed most significantly to accurate and early prediction. Additionally, a web application software was developed to assist clinicians in real-time aneurysm occlusion prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study developed a robust predictive model for UIA occlusion following FD treatment by integrating morphological and hemodynamic parameters, which may provide potentially valuable decision-making support for optimizing treatment strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836316","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":"Correction to “Inhibition of ADORA3 Promotes Microglial Phagocytosis and Alleviates Chronic Ischemic White Matter Injury”","authors":"","doi":"10.1111/cns.70326","DOIUrl":"https://doi.org/10.1111/cns.70326","url":null,"abstract":"<p>In Figure 6, the LFB-stained image in panel M was inadvertently replaced with an incorrect version during figure assembly; the correct version has been provided and does not affect the experimental findings.</p><p>We apologize for this error.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836315","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":"Depletion of HSP60 in Microglia Leads to Synaptic Dysfunction and Depression-Like Behaviors Through Enhanced Synaptic Pruning in Male Mice","authors":"Wenhui Zhu,&nbsp;Jinlong Chang,&nbsp;Liusuyan Tian,&nbsp;Xiuyan Yang,&nbsp;Weifen Li","doi":"10.1111/cns.70394","DOIUrl":"https://doi.org/10.1111/cns.70394","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Microglia, as resident macrophages in the brain, play an important role in depression. Heat shock protein 60 (HSP60), as a chaperone protein, plays a role in cell stress. However, the role of microglial HSP60 in depression remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CX3CR1-CreER was used to generate microglial-specific HSP60 knockout (HSP60 cKO) mice. Behavioral tests, western blotting, Golgi staining, biochemical assays, and proteomics were employed to assess depression-like symptoms, microglial activation, and synaptic changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HSP60 cKO male mice exhibited depressive-like behaviors, without anxiety-like behavior, including increased immobility in the forced swimming and tail suspension tests, reduced sucrose preference, and elevated corticosterone (CORT) levels, indicating HPA axis activation. Microglial activation was confirmed by the increased expression levels of CD68 and CD86, the elevated transcription of the <i>cybb</i> gene, and reduced branch complexity. Enhanced phagocytosis of excitatory synapses, reduced dendritic spine density, and decreased glutamate levels were observed, with downregulation of synaptic proteins (AMPAR2, Synapsin-1, PSD95), indicating dysregulated synaptic pruning. Moreover, GO analysis showed 20 significant differentially expressed proteins (DEPs) from proteomics are associated with the presynaptic endosome, which plays a crucial role in maintaining synaptic function. Treatment with PLX3397, a CSF1R inhibitor, alleviated depressive-like behaviors and restored synaptic density in HSP60 cKO male mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HSP60 deletion in microglia leads to overactivation of microglia, impaired synaptic function, and depression-like behaviors, highlighting the importance of microglial homeostasis in mood regulation and the potential therapeutic role of microglial modulation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70394","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836314","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":"Alleviation of Microglia Mediating Hippocampal Neuron Impairments and Depression-Related Behaviors by Urolithin B via the SIRT1-FOXO1 Pathway","authors":"Cuilan Liu,&nbsp;Di Zhao,&nbsp;Guoxing Yu,&nbsp;HengWei Du,&nbsp;Lihong Xu,&nbsp;Yifan Cao,&nbsp;Minghu Cui,&nbsp;Wentao Wang,&nbsp;Dan Wang,&nbsp;Jing Liu,&nbsp;Fantao Meng,&nbsp;Fengai Hu,&nbsp;Wei Li,&nbsp;Jing Du,&nbsp;Chen Li","doi":"10.1111/cns.70379","DOIUrl":"https://doi.org/10.1111/cns.70379","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Conventional antidepressants exhibit limited efficacy and delayed onset. This study aimed to elucidate the antidepressant effects of urolithin B (UB) and its regulatory role in microglia-mediated hippocampal neuronal dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The mouse model of depression was established using both chronic unpredicted stress (CUS) and lipopolysaccharide (LPS) injection. The therapeutic efficacy of UB was assessed through behavioral paradigms. The microglia activation, cellular cytotoxicity and apoptosis levels, and underlying molecular mechanisms were delineated utilizing proteomics analysis, immunofluorescence staining, real-time PCR and Western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>UB efficiently alleviated depression-related behaviors, accompanied by suppressed microglia activation, neuroinflammation, changes of classic activation (M1)/alternative activation (M2) polarization and recovered sirtuin-1 (SIRT1) and forkhead box protein O1 (FOXO1) expression in the hippocampus. Additionally, UB reduced the cytotoxicity and apoptosis of HT22 cells and depression-related phenotypes treated by the cellular supernatant from LPS-incubated BV2 cells, which was mediated by the SIRT1-FOXO1 pathway. The proteomics analysis of the cellular supernatant content revealed abundant secreting proteins among the LPS/UB application.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study confirmed that microglial SIRT1 mediates UB's antidepressant effects, positioning UB as a promising therapeutic candidate for depression by targeting neuroinflammatory pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836176","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":"Distribution of Intranasally Administered rIL-10 Along the Olfactory Nerve and Perivascular Space After Intracerebral Hemorrhage","authors":"Shaoshuai Wang,&nbsp;Junmin Wang,&nbsp;Xinru Zhang,&nbsp;Shijun Xu,&nbsp;Qinfeng Peng,&nbsp;Yifei Li,&nbsp;Ruoqi Ding,&nbsp;Bing Jiang,&nbsp;Shuyu Wang,&nbsp;Shuaibing Zhang,&nbsp;Siyuan Hu,&nbsp;Yousef Rastegar-Kashkooli,&nbsp;Na Xing,&nbsp;Nan Li,&nbsp;Menglu Wang,&nbsp;Junyang Wang,&nbsp;Xuemei Chen,&nbsp;Chao Jiang,&nbsp;Xiaochong Fan,&nbsp;Jian Wang","doi":"10.1111/cns.70372","DOIUrl":"https://doi.org/10.1111/cns.70372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Rationale</h3>\u0000 \u0000 <p>The utilization of anti-inflammatory therapy for treating brain diseases holds promise; however, research on intranasal administration of drug compounds remains limited. Quantitative data, particularly pharmacokinetics, are scant, and direct evidence of the distribution of intranasally administered recombinant interleukin 10 (rIL-10) within the brain is lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing fluorescent labeling, in vivo imaging, and confocal microscopy, we meticulously monitored the distribution and delivery pathways of intranasally administered rIL-10 in the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate that rIL-10 can permeate the blood–brain barrier and reach the perihematomal area in the striatum of mice with intracerebral hemorrhage. Intranasally administered rIL-10 primarily targets the cerebral cortex, striatum, and thalamus, traversing the olfactory nerve pathway and perivascular space to access these brain regions. This mode of delivery effectively mitigated secondary brain injury after intracerebral hemorrhage. This study contributes to intranasal drug delivery research, offering compelling evidence to support the intranasal delivery of anti-inflammatory cytokines or alternative drug candidates for treating brain diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Efgartigimod for Patients With Myasthenia Gravis in a Real-World Cohort of 77 Patients","authors":"Sijia Hao,&nbsp;Zhe Ruan,&nbsp;Rongjing Guo,&nbsp;Qingqing Wang,&nbsp;Xiaoxi Huang,&nbsp;Chao Sun,&nbsp;Huanhuan Li,&nbsp;Ting Gao,&nbsp;Yonglan Tang,&nbsp;Xiangqi Cao,&nbsp;Yu Liu,&nbsp;Zhuyi Li,&nbsp;Ting Chang","doi":"10.1111/cns.70391","DOIUrl":"https://doi.org/10.1111/cns.70391","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Efgartigimod, a first-in-class neonatal Fc receptor antagonist, is approved for generalized myasthenia gravis (gMG). Its safety and efficacy across MG subtypes remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-center real-world study (September 2023–July 2024) analyzed patients from an MG registry study in China. The primary efficacy outcome is the mean MG-ADL score changes from baseline at weeks 4, 8, and 12, analyzed via generalized estimating equations. Safety was assessed by adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 77 patients (mean age 56.1 ± 15.2 years; 59.7% male), 76 completed at least one treatment cycle (20 completed 2 cycles; 1 completed 3 cycles). After efgartigimod treatment, MG-ADL scores decreased significantly by week 4 (mean difference −6.4, 95% CI −7.2 to −5.6, <i>p</i> &lt; 0.001), sustaining through week 12 (−6.9, −7.8 to −6.1, <i>p</i> &lt; 0.001). After the second cycle, MG-ADL scores at week 12 trended lower than the first cycle (mean difference: −0.8, 95% CI: −2.0 to −0.5, <i>p</i> = 0.061). Efficacy was consistent across MGFA classes and thymoma status. In refractory patients, efgartigimod reduced MG-ADL scores (<i>p</i> &lt; 0.001). Adverse events occurred in 3.9% (3/77).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Efgartigimod safely improved MG-ADL scores and reduced steroid use across MG subtypes, with sustained efficacy through multiple treatment cycles. These findings support its potential when conventional therapies fail.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835939","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":"Dual Role of Exosomes in Parkinson's Disease: Adenine Exerts a Beneficial Effect","authors":"Lei Chen,&nbsp;Yi-Ting Shao,&nbsp;Ji Geng,&nbsp;Hua Liu,&nbsp;Qing-Shan Liu,&nbsp;Yong Cheng,&nbsp;Ting Sun","doi":"10.1111/cns.70331","DOIUrl":"https://doi.org/10.1111/cns.70331","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Developing validated treatments for Parkinson's disease (PD) remains a priority for clinicians and researchers. The lack of viable therapies may stem from an incomplete understanding of PD pathogenesis and inadequate therapeutic candidates. The production and transmission of exosomes are gaining recognition in the pathogenesis of neurodegenerative diseases. However, how exosomes affect the pathophysiology of PD has not been well elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we investigated the effect of exosomes secreted by rats that were treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) in treating healthy or PD model mice, and we evaluated the efficacy of peripheral and intracranial administration of adenine, which is an exosomal metabolite identified through widely targeted metabolomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that exosomes derived from the blood of healthy rats alleviated motor dysfunction, dopaminergic neuron loss in the substantia nigra pars compacta and striatum, oxidative injury, and neuroinflammation. Conversely, exosomes from the blood of PD model rats reproduced the behavioral phenotype and pathology of PD in healthy mice. Additionally, peripheral and intracranial administration of adenine ameliorated the motor coordination disorder and dopaminergic neuron loss, and maintained the homeostasis of oxidative stress and neuroinflammation by activating cAMP/PKA signaling in PD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Together, these findings shed light on the mechanism by which exosomes participate in the pathophysiology of PD by transmitting the metabolite adenine and providing potential therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835938","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":"Repeated Exposure to Sevoflurane in Neonatal Mice Induces Cognitive and Synaptic Impairments in a TTLL6-Mediated Tubulin Polyglutamylation Manner","authors":"Yang Yu,&nbsp;Yue Zhao,&nbsp;Jingyu Feng,&nbsp;Naqi Lian,&nbsp;Jiafeng Yu,&nbsp;Yongyan Yang,&nbsp;Junyan Yao,&nbsp;Yonghao Yu","doi":"10.1111/cns.70376","DOIUrl":"https://doi.org/10.1111/cns.70376","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Repeated sevoflurane exposure during the neonatal stage may induce Tau phosphorylation, dendritic spine loss, and neurocognitive impairment in the developing brain. Tubulin tyrosine ligase like-6 (TTLL6), which aggregates in dendrites due to Tau missorting, regulates microtubule stability via α-tubulin polyglutamylation. Meanwhile, Spastin modulates dendritic spine formation by severing microtubules. We hypothesize that repeated sevoflurane treatment impairs dendritic spine remodeling in neonatal mice by enhancing TTLL6-mediated tubulin polyglutamylation and increasing Spastin expression, leading to cognitive dysfunction in their pre-adolescent stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Six-day-old wild type (WT), TTLL6 brain conditional knockout (TTLL6_CKO), TTLL6-flox (TTLL6_CON) and Tau-knockout mice were treated with 3% sevoflurane for 2 h daily on postnatal days (P) 6, 8, and 10. Levels of Tau, phosphorylated Tau (pTau), TTLL6, polyglutamylated tubulin, ATP, Spastin, PSD95, Tau-TTLL6 interaction, Tau-TTLL6 missorting, dendritic spine remodeling, and behavioral alterations were compared across these groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Repeated sevoflurane exposure during brain development in neonatal mice could reduce dendritic spine density, synapse number, PSD95, and ATP levels, while increasing pTau, polyglutamylated tubulin, Tau-TTLL6 missorting from axons to the somatodendritic compartment, and Spastin levels, leading to cognitive impairment later in their pre-adolescent stage (P30). However, these changes were ameliorated in the TTLL6_CKO mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Repeated neonatal sevoflurane exposure results in synaptic impairment through TTLL6-mediated tubulin polyglutamylation and increased Spastin expression, causing pre-adolescent cognitive dysfunction in mice. This process is initiated by Tau phosphorylation and missorting from axons to somatodendritic compartments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801313","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}