CNS Neuroscience & Therapeutics最新文献

{"title":"Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals","authors":"Hongbin Wang,&nbsp;Cong Chen,&nbsp;Yuting Lin,&nbsp;Zhifeng Tian,&nbsp;Zihan Yan,&nbsp;Xuan Zeng,&nbsp;Yantao Yang,&nbsp;Meiyu Lin,&nbsp;Qidi Ai,&nbsp;Xuan Liu,&nbsp;Songwei Yang,&nbsp;Naihong Chen","doi":"10.1111/cns.70600","DOIUrl":"https://doi.org/10.1111/cns.70600","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Depression is a common mental illness with a high relapse rate, which has a serious negative impact on national economic development and happiness. At present, the pathogenesis of depression is still unclear, and there are inevitable limitations in first-line clinical treatment. Therefore, it is very important to clarify the pathological mechanism of depression for the development of safe and effective antidepressants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In recent years, considerable research has shown that connexin43 (Cx43) and its regulated astrocyte gap junction (GJ) dysfunction are closely related to the occurrence and development of depression. This review aims to summarize the mechanisms by which Cx43 and its-mediated astrocytic GJs contribute to depression progression, focusing on their regulatory roles in transmitting electrical signals (K⁺, Ca²⁺) and chemical signals (neurotransmitters, inflammatory factors). This work provides theoretical foundations for elucidating the pathological mechanisms of depression and developing novel antidepressant therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Cx43 and the gap junctions it regulates in astrocytes play a pivotal role in the pathophysiology of depression by influencing both electrical and chemical signaling between neurons. Further investigation into its mechanisms may offer novel therapeutic approaches for depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998722","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":"Headache in Patients With Non-Thrombotic Internal Jugular Vein Stenosis: Clinical Characteristics and Associated Risk Factors in a Retrospective Study of 283 Cases","authors":"Guangyu Han,&nbsp;Shuling Wan,&nbsp;Xunming Ji,&nbsp;Ran Meng,&nbsp;Da Zhou","doi":"10.1111/cns.70594","DOIUrl":"https://doi.org/10.1111/cns.70594","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to characterize the clinical features of headache in patients with non-thrombotic internal jugular vein stenosis (IJVS) and to identify associated risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study consecutively enrolled patients with imaging-confirmed non-thrombotic IJVS from January 2021 through July 2024. Participants were divided into IJVS-headache and IJVS-without-headache groups based on clinical symptoms. Demographic, clinical, neuroimaging, and treatment data were reviewed in detail. Univariate and multivariate logistic regression analyses were performed to determine risk factors for headache.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 283 eligible patients (median age: 51 years in the IJVS-headache group vs. 56 years in the IJVS-without-headache group, <i>p</i> &lt; 0.001), 65.02% reported headache. Most headaches were chronic (82.07%), generalized (85.87%), and moderate in intensity (53.26%), with notable daily life impact (57.61%). Univariate analysis showed that headache was significantly associated with visual disturbances (<i>p</i> = 0.010), elevated cerebrospinal fluid opening pressure (<i>p</i> &lt; 0.001), high jugular bulb (<i>p</i> = 0.007), and severe scalp vein dilation (<i>p</i> &lt; 0.001), but inversely associated with severe vertebral vein expansion (<i>p</i> &lt; 0.001). Multivariate regression revealed that high jugular bulb (OR = 3.144, 95% CI: 1.083–9.123, <i>p</i> = 0.035), severe scalp vein dilation (OR = 2.142, 95% CI: 1.068–4.294, <i>p</i> = 0.032), and protein C or S deficiency (OR = 5.984, 95% CI: 1.196–29.928, <i>p</i> = 0.029) were independent risk factors, whereas severe vertebral vein expansion was protective (OR = 0.184, 95% CI: 0.092–0.366, <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Headache represents a prevalent and often disabling symptom in non-thrombotic IJVS, underpinned by distinctive vascular and hematologic profiles. Identification of high-risk patients based on neuroimaging and thrombophilia screening may facilitate personalized interventions and improve symptom control.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935073","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":"Reorganization of Mitochondrial Function and Architecture in Response to Plant-Derived Alkaloids: Anatabine, Anabasine, and Nicotine, Investigated in SH-SY5Y Cells and in a Cellular Model of Parkinson's Disease","authors":"Dominika Malińska,&nbsp;Karolina Drabik,&nbsp;Bernadeta Michalska,&nbsp;Jarosław Walczak,&nbsp;Małgorzata Partyka,&nbsp;Monika Prill,&nbsp;Jędrzej Szymański,&nbsp;Paulina Patalas-Krawczyk,&nbsp;Karolina Piecyk,&nbsp;Jerzy Duszyński,&nbsp;Mariusz R. Więckowski,&nbsp;Joanna Szczepanowska","doi":"10.1111/cns.70571","DOIUrl":"https://doi.org/10.1111/cns.70571","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Nicotine, anatabine, and anabasine are the most prevalent alkaloids in <i>Nicotiana</i> species. While nicotine is the main addictive ingredient in tobacco products, it was also shown to have neuroprotective properties. Mitochondria appear to be one of the targets of nicotine in the cell. These multifunctional organelles are also the first responders to various cellular stresses. Thus, we characterized the impact of tobacco alkaloids on these organelles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the effects of structurally similar alkaloids, anatabine, anabasine, and nicotine, on mitochondrial function in SH-SY5Y neuroblastoma cells under basal conditions and in the presence of rotenone, a mitochondrial stressor commonly used to model the cellular pathology underlying Parkinson's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed changes in mitochondrial behavior, including hyperpolarization, alterations in mitochondrial network morphology, increased mitochondrial turnover rates, and upregulation of mitochondrial biogenesis regulators. The profiles of changes induced by particular alkaloids slightly differed; however, they shared many features with the stress response observed upon treatment with rotenone. Interestingly, the effects of the alkaloids and rotenone were not additive. Moreover, some parameters altered by rotenone were normalized upon cotreatment with the alkaloids.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The results indicate that the investigated alkaloids stimulate mitochondrial stress adaptation. Despite structural similarity, they act through slightly different mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935070","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":"ApoE4 Upregulates GSK-3β to Aggravate Alzheimer-Like Pathologies and Cognitive Impairment in Type 2 Diabetic Mice","authors":"Yuying Wang,&nbsp;Yang Gao,&nbsp;Yarong Wang,&nbsp;Fuqiang Zhang,&nbsp;Fei Sun,&nbsp;Xin Wang,&nbsp;Jiazhao Xie,&nbsp;Zhipeng Xu,&nbsp;Junjian Zhang,&nbsp;Haibo Xu,&nbsp;Yao Zhang,&nbsp;Jian-Zhi Wang","doi":"10.1111/cns.70575","DOIUrl":"https://doi.org/10.1111/cns.70575","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The apolipoprotein E (ApoE) ε4 allele and type 2 diabetes mellitus (T2DM) are independent risk factors for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder in the elderly. The T2DM patients carrying the ApoE ε4 allele exhibit heightened activation of platelet glycogen synthase kinase-3β (GSK-3β), a key downstream kinase in the insulin signaling pathway, along with more severe cognitive deficits. This observation suggests an intrinsic link between ApoE ε4, GSK-3β, and cognitive dysfunction. However, the precise mechanisms by which ApoE ε4 influences GSK-3β activity and exacerbates brain pathology and cognitive decline in T2DM patients remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate these mechanisms, we developed T2DM mouse models by generating humanized ApoE ε3/ε3 and ε4/ε4 knock-in mice. The mice were subjected to a high-fat diet combined with multiple low-dose intraperitoneal streptozotocin injections to induce T2DM. We then assessed GSK-3β expression, AD-like pathologies, and cognitive functions in these models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that GSK-3β activity was significantly upregulated in ApoE4 mice, accompanied by disruption of the insulin signaling pathway. Notably, ApoE4-T2DM mice exhibited exacerbated AD-related pathologies, including increased accumulation of hyperphosphorylated tau, neuroinflammation, and synaptic loss. These changes were correlated with more severe cognitive impairments compared with ApoE3-T2DM or ApoE4 mice. Furthermore, inhibition of GSK-3β activity using the selective inhibitor 9-ING-41 effectively ameliorated both AD-like pathologies and cognitive deficits in ApoE4-T2DM mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that ApoE4 exacerbates AD pathogenesis by activating GSK-3β. Furthermore, targeting GSK-3β may offer a promising therapeutic strategy to halt the progression from T2DM to AD, providing new insights into potential interventions for patients at risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935367","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":"Intravenous Thrombolysis in Acute Ischemic Stroke: A Prognostic Prediction Model and the Role of Ischemic Core Growth Rate","authors":"Yipeng Yu,&nbsp;Lulu Zhang,&nbsp;Qi Fang","doi":"10.1111/cns.70589","DOIUrl":"https://doi.org/10.1111/cns.70589","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The tissue window is increasingly recognized in guiding reperfusion therapy beyond the standard time window in acute ischemic stroke (AIS). This study aims to develop a nomogram incorporating an ischemic core growth rate index to provide individualized prediction of neurological outcomes in AIS patients who received intravenous thrombolysis (IVT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective study was conducted at the First Affiliated Hospital of Soochow University (2016–2023). A lasso-logistic method was employed for variable selection and model construction. The performance of the model was evaluated using the receiver operating characteristic curve, calibration curve, decision curve analysis, and compared with a conventional indexed one.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study cohort comprised 553 patients with favorable outcomes (median ischemic core growth rate: 1.4 [0.5, 4.1] mL/h) and 198 patients with poor outcomes (median ischemic core growth rate: 5.7 [1.1, 14.2] mL/h). The nomogram included diabetes, TOAST classification, ischemic core growth rate, neutrophil count, direct bilirubin, and NIHSS score at admission. It achieved an AUC of 0.882 (95% CI: 0.855–0.908), outperforming the conventional indexed one. Calibration showed good agreement between predicted and observed outcomes (Hosmer–Lemeshow <i>p</i> = 0.851).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ischemic core growth rate strongly correlates with neurological prognosis in AIS. This nomogram offers reliable predictions for IVT outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70589","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934968","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":"Electroacupuncture Pretreatment Alleviates Myocardial Ischemia–Reperfusion Injury by Inhibiting Engulfment by Microglia in the Lateral Hypothalamus","authors":"Xiang Zhou,&nbsp;Peiyi Yang,&nbsp;Chaonan Dong,&nbsp;Huimin Chang,&nbsp;Fan Zhang,&nbsp;Qi Shu,&nbsp;Naixuan Wei,&nbsp;Bin Zhang,&nbsp;Yan Wu,&nbsp;Wenjing Shao,&nbsp;Ronglin Cai,&nbsp;Qing Yu","doi":"10.1111/cns.70595","DOIUrl":"https://doi.org/10.1111/cns.70595","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The occurrence of myocardial ischemia–reperfusion injury (MIRI) is accompanied by neuroinflammatory reactions and is closely related to the overactivation of microglia. Currently, effective clinical strategies to prevent MIRI are unclear. This study investigated potential therapeutic targets and the mechanisms of electroacupuncture pretreatment (EA-pre) for MIRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A MIRI mouse model was established by ligating the left anterior descending branch of the heart for 30 min and reperfusion for 2 h. The mechanisms by which EA-pre alleviates MIRI were investigated through immunofluorescence staining, chemogenetics, and fiber photometry recordings, focusing on the potential involvement of microglia and glutamate (Glu) neurons in the lateral hypothalamic (LH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>EA-pre improves cardiac function in MIRI mice by suppressing microglial activation in the LH. The underlying mechanism likely involves EA-pre inhibition of microglial engulfment of inhibitory synapses around LH^Glu neurons. Targeted activation of LH^microglia reverses EA's inhibitory effect, thereby increasing LH^Glu neuronal activity and triggering overactivation of the sympathetic nervous system (SNS), which ultimately exacerbates MIRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EA-pre inhibits microglial engulfment of inhibitory synapses around LH^Glu neurons in MIRI mice, thereby suppressing LH^Glu neuronal activity, reducing SNS output, and ultimately exerting cardioprotective effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70595","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934969","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":"Parietal rTMS Induced Changes in Cortical Excitability in Patients With Minimally Conscious State Using TMS-EEG","authors":"Ye Zhang,&nbsp;Xiaoping Wan,&nbsp;Yong Wang,&nbsp;Xiaoli Li,&nbsp;Jubao Du,&nbsp;Xiao Yan,&nbsp;Zilong Zhu,&nbsp;Yanhua Li,&nbsp;Weiqun Song","doi":"10.1111/cns.70583","DOIUrl":"https://doi.org/10.1111/cns.70583","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To verify the effectiveness of the parietal repetitive transcranial magnetic stimulation (rTMS) and take advantage of TMS-EEG to assess cortical excitability in patients with minimally conscious states (MCS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled 10 MCS patients who received 10 sessions of 10 Hz rTMS on the parietal cortex for 10 consecutive days and then 10 days of sham stimulation after a 14-day wash-out period. The Coma Recovery Scale-Revised (CRS-R) and TMS-EEG were used to assess the levels of consciousness and cortical excitability before and after active and sham stimulation, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to sham stimulation, the CRS-R revealed a significant improvement after receiving active rTMS. The amplitude of components of TMS-evoked potential after active stimulation significantly increased at 30, 60, and 180 ms, respectively; global brain power increased significantly. The PCIst values had a significant difference after active rTMS stimulation, and the CRS-R scores showed a significant correlation with PCIst values before and after active stimulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>High-frequency rTMS on the parietal cortex has therapeutic efficacy and can improve cortical excitability in MCS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Our results provide preliminary evidence to support the use of the parietal area as a potential therapeutic target for MCS patients in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935072","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":"The Change of Noncoding RNA Expression in Olfactory Bulb of Hepatic Encephalopathy Mouse Model: Transcriptomic Analysis and Cellular Analysis","authors":"Young-Kook Kim,&nbsp;Sujung Yeom,&nbsp;Seo Yoon Choi,&nbsp;Yeongseo Ryu,&nbsp;Dahee Jeong,&nbsp;Danbi Jo,&nbsp;Dong Hoon Lee,&nbsp;Juhyun Song","doi":"10.1111/cns.70596","DOIUrl":"https://doi.org/10.1111/cns.70596","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Hepatic encephalopathy (HE) is a neuropsychiatric disorder associated with cirrhosis and chronic liver disease primarily driven by ammonia (NH3) toxicity, which leads to neuroinflammation and cognitive deficits. Recent studies have identified olfactory dysfunction as a potential early indicator of HE, linked to ammonia-induced neurotoxicity in the brain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After confirming physiological alterations in olfactory cells induced by ammonia, we assessed gene expression changes in olfactory bulbs of bile duct ligation (BDL) mice as an HE mouse model. We systematically profiled diverse coding and noncoding RNAs (ncRNAs) associated with olfactory dysfunction in HE and analyzed the functional implications based on transcriptomic signatures. We also compared ammonia toxicity effects between the olfactory bulb and cerebral cortex in this animal model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Furthermore, we investigated the differential impacts on the olfactory bulb between HE and high-fat diet-induced models, two major paradigms of metabolic imbalance. We identified key RNAs commonly altered between the olfactory bulb and cerebral cortex of the HE model, as well as in olfactory bulbs across BDL and high-fat diet models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results provide a transcriptomic resource for understanding the molecular landscape of HE-related olfactory dysfunction and may inform future studies aimed at functional validation and therapeutic exploration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Neurodegenerative Disease Therapy: Stem Cell Clinical Trials and Promise of Engineered Exosomes","authors":"Sevim Isik,&nbsp;Sajeda Osman,&nbsp;Bercem Yeman-Kiyak,&nbsp;Suhair Rami Mohammed Shamshir,&nbsp;Nesrin Majdi Edwan Sanchez","doi":"10.1111/cns.70577","DOIUrl":"https://doi.org/10.1111/cns.70577","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This review provides a systematic evaluation of 94 stem cell clinical trials to treat neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were collected from using relevant search terms, focusing exclusively on stem cell therapy. Of the 8000+ participants in these trials, nearly 70% were enrolled in AD-related studies. Only three Phase 3 studies were conducted, and most trials were in the early phases (Phases 1 and 2). Mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, and embryonic stem cells are used the most to treat neurodegenerative diseases. This review also explores the emerging fields of preclinical and clinical investigations of stem cell-derived exosome-based therapies for neurodegenerative diseases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Exosomes can cross the blood–brain barrier to deliver therapeutic molecules directly to the brain, offering a less invasive alternative to stem cell transplantation. Mesenchymal stem cell-derived exosomes, in particular, have demonstrated significant potential in preclinical models by reducing neuroinflammation, oxidative stress, and promoting neuronal regeneration. Additionally, recent advances in exosome engineering, including surface modifications, therapeutic agent loading, and transgenic modifications, have improved targeting, stability, blood–brain barrier delivery, and neural cell interactions, enabling targeted and effective treatment. Exosome-based therapies are in the preliminary phases of clinical investigation, with only three clinical trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Given the increasing interest in exosome therapy, clinical investigations are expected to increase. This growth will be driven by ongoing advancements in exosome technology, a deeper understanding of their therapeutic potential, and escalating demand for innovative treatment strategies for neurodegenerative diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935250","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":"The Microbiota-Gut-Brain Connection: A New Horizon in Neurological and Neuropsychiatric Disorders","authors":"Md. Faysal,&nbsp;Mehrukh Zehravi,&nbsp;Baishakhi Sutradhar,&nbsp;Md Al Amin,&nbsp;Thukani Sathanantham Shanmugarajan,&nbsp;Uppuluri Varuna Naga Venkata Arjun,&nbsp;Susithra Ethiraj,&nbsp;Akiladevi Durairaj,&nbsp;Girija Dayalan,&nbsp;Shaik Khadeer Ahamad,&nbsp;Safia Obaidur Rab,&nbsp;Kannan Raman,&nbsp;Talha Bin Emran","doi":"10.1111/cns.70593","DOIUrl":"https://doi.org/10.1111/cns.70593","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The microbiota-gut-brain axis (MGBA), a complex two-way connection between the gut microbiota and the brain, has become a key regulator of neurological and neuropsychiatric disorders. Neurological disorders and gut microbiota dysbiosis are linked to these diseases. Changes in gut microbiota can lead to neurotransmitter imbalances, oxidative stress, and neuroinflammation. Gut dysbiosis may contribute to the development of diseases such as depression, autism, schizophrenia, bipolar disorder, Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, epilepsy, anxiety, and autism spectrum disorders through immunological regulation, neuroinflammation, and neurotransmitter metabolism changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This review systematically sourced articles related to microbiota gut brain axis, neurological disorders, neuropsychiatric disorders and clinical studies from major medical databases, including Scopus, PubMed, and Web of Science.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review explores the molecular processes underlying MGBA interactions, including vagus nerve signaling, systemic immunological responses, and metabolites produced by microorganisms. The discussion explores the potential of microbiome-targeted treatments like fecal microbiota transplantation, probiotics, and prebiotics as effective treatment methods. The comprehension of the MGBA can revolutionize neurology and psychiatry, introducing innovative diagnostic and therapeutic approaches. Multiple elements, including diet, metabolism, age, stress, and medications, shape the human gut microbiota, and intestinal imbalances can lead to CNS diseases. The MGBA interacts with gut bacteria, and gut dysbiosis is associated with neurological disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The review demonstrates the correlation between gut microbiota and neurologically associated diseases, highlighting its importance in neurogenesis, mental development, emotions, and behaviors. MGBA, mediated by microbial metabolites, affects brain function and neuroinflammation. Interventions like fetal microbiota transplantation, probiotics, and prebiotics can improve microbial balance, but more clinical research is needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998664","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}