CNS Neuroscience & Therapeutics最新文献

{"title":"Disrupted Brain Structure–Function Coupling and Its Mediating Effects on the Associations Between Cerebral Small Vessel Disease Burden and Cognitive Dysfunction","authors":"Na Wang,&nbsp;Lingfei Guo,&nbsp;Yian Gao,&nbsp;Chaofan Sui,&nbsp;Xinyue Zhang,&nbsp;Yuanyuan Wang,&nbsp;Yajie Fu,&nbsp;Nan Zhang,&nbsp;Yena Che,&nbsp;Hongwei Wen,&nbsp;Changhu Liang","doi":"10.1111/cns.70604","DOIUrl":"10.1111/cns.70604","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>We aimed to specify relationships among cerebral small vessel disease (CSVD) burden, cognitive dysfunction, and brain structure–function coupling changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 108 patients with mild CSVD burden (CSVD-m), 53 patients with severe CSVD burden (CSVD-s), and 76 healthy controls (HC) were included in this study. The ratio of regional homogeneity (ReHo) or amplitude of low-frequency fluctuation (ALFF) to gray matter volume (GMV) was calculated as an indicator of voxel-wise structure–function coupling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significantly decreased or increased ReHo–GMV and ALFF–GMV coupling values in patients with severe CSVD burden were primarily found in several brain regions, and the disrupted structure–function coupling in the right putamen mediated the relationship between CSVD burden and cognitive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Brain structure–function coupling characterized by ReHo–GMV and ALFF–GMV mediated the cognitive dysfunction caused by CSVD and was an innovative and effective brain imaging indicator for exploring the association between CSVD burden and cognitive dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079191","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":"Perinatal Maturation of Drug Transporters and Claudin-5 at the Blood–Brain Barrier","authors":"Laetitia Federici,&nbsp;Salvatore Cisternino,&nbsp;Sylvain Auvity,&nbsp;Antoinette Gelot,&nbsp;Mathilde Becmeur-Lefebvre,&nbsp;Maryline Favier,&nbsp;Gaelle Letort,&nbsp;Philippe Mailly,&nbsp;Martine Cohen-Salmon,&nbsp;Anne-Cécile Boulay","doi":"10.1111/cns.70614","DOIUrl":"10.1111/cns.70614","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cerebral capillary endothelial cells (EC) form the blood–brain barrier (BBB), which regulates molecular exchange between the blood and the brain. Understanding their function during brain development is essential for optimizing treatments in neonates, children, as well as pregnant and breastfeeding women.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>P-glycoprotein (P-gp/ABCB1) expression during brain development was assessed by immunohistochemistry in human cortical samples. In mice, postnatal brain microvessels were analyzed using qPCR and Western Blot, and BBB function was evaluated in vivo using [¹⁴C]sucrose to assess barrier integrity, and [³H]verapamil or [³H]rosuvastatin to assess transport activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In humans, P-gp reached mature levels in the early postnatal period. In mice, BBB integrity was established by postnatal day 5 (P5), but the expression of claudin-5, P-gp, and Oatp1a4 increased until P30. Brain transport of verapamil and rosuvastatin significantly decreased between P15 and P30, indicating enhanced efflux capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although BBB integrity is established at birth, BBB continues maturing throughout the postnatal period, with a predominant efflux transport. Our findings underscore the critical role of P-gp in the acquisition of BBB gatekeeper properties. The immature BBB may result in a higher brain susceptibility to P-gp substrates in preterm infants.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70614","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145084549","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":"ARIP1 Deficiency Facilitates the Inhibition of Neuronal Ferroptosis in Cerebral Ischemia by Activin A Through SMAD3 and p38 MAPK Signaling","authors":"Zhulin Zou,&nbsp;Yunhan Zhang,&nbsp;Chenmeng Guo,&nbsp;Xinyao Qie,&nbsp;Daqing Xie,&nbsp;Lerong Wang,&nbsp;Zhonghui Liu,&nbsp;Haiyan Liu","doi":"10.1111/cns.70615","DOIUrl":"10.1111/cns.70615","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Ferroptosis is an essential pathophysiological process in cerebral ischemic injury. Activin receptor-interacting protein 1 (ARIP1) is a negative regulator of the activin signaling pathway in neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigated whether activin A inhibits neuronal ferroptosis and the role of ARIP1 in cerebral ischemic injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>In this study, activin A increased the viability of primary neurons under conditions of oxygen–glucose deprivation (OGD). Subsequent RNA-sequencing analysis of activin A-treated neurons identified expression of <i>Slc7a11</i> as the ferroptosis-associated gene with significant upregulation. Next, using the CRISPR/Cas9 system, mice were generated with a heterozygous deficiency of ARIP1 (<i>Arip1</i>^<i>−/+</i>), and the results revealed that the expression of GPX4 was markedly elevated and SLC7A11 was reduced in OGD-treated <i>Arip1</i>^<i>−/+</i> neurons, compared with that in wild-type (WT) neurons, which was accompanied by an increase of p-SMAD3 and a decrease of p-p38 MAPK levels. In addition, our data showed that activin A activated SMAD3 and inhibited p38 MAPK phosphorylation, which differentially modulated SLC7A11 and GPX4 expression, ultimately suppressing OGD-induced ferroptosis. Notably, <i>Arip1</i>^<i>−/+</i> mice showed an improvement in neurological deficits and reduced cerebral infarction in the permanent middle cerebral artery occlusion (pMCAO) model. Furthermore, we observed that activin A exerted similar protective effects against ischemic injury in <i>Arip1</i>^<i>−/+</i> mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings indicate that downregulating the expression of ARIP1 suppresses neuronal ferroptosis by modulating SLC7A11/GPX4 expression via SMAD3 and p38 MAPK signaling, ultimately enhancing the neuroprotective role of activin A against cerebral ischemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079184","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":"Bilirubin Alleviates Spinal Cord Injury by Enhancing SOCS3-Mediated Anti-Inflammatory Effects via Gas6-Axl Signaling","authors":"Kun-Mao Jiang,&nbsp;Ya-Qi Luan,&nbsp;Na Shen,&nbsp;Xiu-Ting Qi,&nbsp;Liang Hu,&nbsp;Yu Wang,&nbsp;Wen-Tao Liu,&nbsp;Rong Wang,&nbsp;Tong-Tong Lin,&nbsp;Da-Yong Peng","doi":"10.1111/cns.70538","DOIUrl":"10.1111/cns.70538","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Many studies have emphasized the role of microglia-mediated neuroinflammation in spinal cord injury (SCI); however, effective clinical targets remain elusive. The growth arrest-specific 6 (Gas6)/Axl receptor tyrosine kinase (Axl) signaling pathway has been implicated in reducing inflammation, promoting tissue repair, and functional recovery. Here, we elucidate the importance of the Gas6-Axl signaling pathway in SCI repair and evaluate the role of bilirubin in modulating Gas6-Axl signaling after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>SCI mice model was used to investigate the effects of bilirubin treatment on inflammation and motor function recovery. Additionally, Gas6-deficient (<i>Gas6</i>^<i>−</i><i>/</i>^<i>−</i>) mice and wild-type (WT) mice were employed to examine the role of Gas6-Axl signaling in SCI recovery. Microglial cells were cultured to assess the effects of bilirubin on the activation of the Gas6-Axl-SOCS3 signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>Gas6</i>^<i>−</i><i>/</i>^<i>−</i> mice exhibited increased mortality, severe locomotor deficits, and impaired neuromuscular activity compared to WT mice. Bilirubin treatment in SCI models facilitated recovery by upregulating Gas6-Axl signaling, which in turn enhanced SOCS3 expression and suppressed the expression of pro-inflammatory mediators such as IL-1β and MMP-9. Furthermore, bilirubin treatment reduced microglial activation, highlighting its neuroprotective and anti-inflammatory properties.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study underscores the importance of the Gas6-Axl-SOCS3 axis in regulating functional recovery and inflammation after SCI. Activation of the Gas6-Axl pathway, particularly when combined with bilirubin treatment, represents a promising therapeutic strategy for mitigating SCI-induced damage and improving functional outcomes. Given their central role in both the pathogenesis and resolution of SCI, bilirubin treatment emerges as a promising clinical therapeutic drug for SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12441303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074021","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":"How to Improve Cognitive Flexibility: Evidence From Noninvasive Neuromodulation Techniques","authors":"Naeimeh Akbari Gharalari,&nbsp;Solmaz Fallahi,&nbsp;Elnaz Nakhjiri,&nbsp;Leila Hosseini,&nbsp;Saba Pakkhou,&nbsp;Naser Havaei,&nbsp;Sina Khodakarimi,&nbsp;Parviz Shahabi,&nbsp;Mohsen Jafarzadeh Gharehziaaddin,&nbsp;Hamid Soltani Zangbar","doi":"10.1111/cns.70613","DOIUrl":"10.1111/cns.70613","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cognitive flexibility (CF) is a core component of executive function that enables humans to adaptively process and respond effectively to diverse and dynamic contextual needs. The execution of CF-related tasks depends on the collective interaction of various neural circuits in essential brain regions, such as the prefrontal, anterior cingulate, and posterior parietal cortices, which support the harmonic and smooth transition of thoughts and perspectives. Therefore, clarifying the mechanism of CF and introducing non-invasive neuromodulatory methods that enhance CF provides a way for developing new treatment approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This review systematically investigates the application of photobiomodulation (PBM), neurofeedback (NF), repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and virtual reality (VR) as non-invasive neuromodulatory techniques for modulating cognitive behaviors related to CF in neuropsychological conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Considering the vital role of CF in executive functions, deficits in CF impair adaptive behavior in neuropsychological conditions such as schizophrenia, autism spectrum disorder (ASD), and age-related cognitive decline. Some technology-based interventions, including PBM, NF, rTMS, tDCS, and VR, have been developed to non-invasively modulate the switching capability and strategies of the mind. These non-invasive interventions provide targeted neuromodulation on neural circuits and have demonstrated a promising effect in improving cognitive processes, including CF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present study provides a comprehensive review of the therapeutic consequences of non-invasive neuromodulatory methods on CF in neurological conditions. This insight can offer a perspective for planning various research strategies and clinical approaches aimed at improving CF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068693","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-Functionalized Extracellular Vesicles Promote Brain Repair and Remodeling Following Ischemic Stroke in Mice","authors":"Victoria Shi,&nbsp;Shengju Wu,&nbsp;Qianyuan Lian,&nbsp;Rubing Shi,&nbsp;Ze Liu,&nbsp;Tongtong Xu,&nbsp;Shiyu Deng,&nbsp;Xinfa Shao,&nbsp;Anja Beckmann,&nbsp;Wanlu Li,&nbsp;Yaohui Tang,&nbsp;Carola Meier,&nbsp;Guo-Yuan Yang,&nbsp;Zhijun Zhang","doi":"10.1111/cns.70597","DOIUrl":"10.1111/cns.70597","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ischemic stroke remains a leading cause of long-term disability and mortality worldwide, with few effective treatment options. A key challenge in recovery is the brain's limited capacity to regenerate neurovascular structures after injury. To address this, we developed a dual-functionalized extracellular vesicle (EV) platform designed to enhance both targeting specificity and therapeutic efficacy for post-stroke repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Neural stem cell-derived EVs were bioengineered via bio-click chemistry to display RGD peptides, enabling selective binding to integrin αVβ3, which is upregulated on activated endothelial cells in ischemic regions. EVs were concurrently loaded with vascular endothelial growth factor (VEGF), a pro-angiogenic and neurogenic cytokine that also enhances αVβ3 expression—thus creating a synergistic positive feedback mechanism to amplify targeting and tissue repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Engineered EVs retained normal morphology and showed a 5.2-fold increase in endothelial uptake compared to naïve EVs (<i>p</i> &lt; 0.01). In vitro, they significantly enhanced endothelial cell migration by 2.1-fold (<i>p</i> &lt; 0.05). In a mouse model of transient middle cerebral artery occlusion (tMCAO), intravenously delivered dual-functionalized EVs preferentially accumulated in the ischemic hemisphere, reduced infarct volume by 52.4%, and improved motor coordination (rotarod latency) by 71.8% compared to PBS-treated controls (<i>p</i> &lt; 0.05). Immunostaining revealed enhanced CD31+ microvessel density and increased Nestin+ neural stem and progenitor cell presence, indicating promotion of both angiogenesis and neurogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study presents a dual-functionalized EV system that combines targeted delivery with therapeutic reinforcement through VEGF loading, offering a potent and synergistic approach for ischemic stroke repair. These findings support further translational development of engineered EVs for neurovascular regeneration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12437317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068764","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":"Metabolic Factors Related to Interpersonal Dysfunction in Acromegaly: A Nationwide Cross-Sectional Study in China","authors":"Shashi Kiran Tagilapalli,&nbsp;Zongming Wang,&nbsp;Yuechu Lucinda Lu,&nbsp;Guofeng Zhang,&nbsp;Weijie Su,&nbsp;Zhentian Wu,&nbsp;Jiaming Wang,&nbsp;Qing Rao,&nbsp;Haijun Wang,&nbsp;Dongsheng He,&nbsp;Yonggao Mou,&nbsp;Shun Yao,&nbsp;Yanmei Tie,&nbsp;Wenli Chen","doi":"10.1111/cns.70607","DOIUrl":"10.1111/cns.70607","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To identify the clinical manifestations, metabolic factors, and comorbidities independently associated with interpersonal dysfunction in Chinese acromegaly patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed clinical, cognitive, and comorbidity data from 585 acromegaly patients across 112 tertiary hospitals in China (July 1995–December 2018). Interpersonal difficulties were quantified using the Inventory of Interpersonal Problems-Distress (IIP-D) and dichotomized into low (&lt; 17) and high (≥ 17) groups. Group differences were tested with nonparametric tests. Supervised machine-learning models were developed to predict features associated with the high IIP-D group, with performance evaluated via five-fold cross-validation. The top-performing model was further validated on the held-out data set and the feature importance analysis identified the key predictors. Exploratory hierarchical clustering (Ward's method) was used to explore symptom groupings, though sampling adequacy was limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with high interpersonal distress exhibited significantly higher preoperative growth hormone (GH), frontal bossing, palpitations, and cognitive impairment (all <i>p</i> &lt; 0.05). Among machine-learning models, extreme gradient boosting (XGBoost) demonstrated the highest performance, area under the curve (AUC = 0.868 in across-validation), and maintained strong accuracy in final testing (AUC = 0.873). Key independent predictors included frontal bossing, palpitations, cardiomyopathy, disease duration, preoperative GH, acral enlargement, arrhythmia, and atrial fibrillation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Physical disfigurement, palpitations, cardiac comorbidities, and elevated GH levels independently predict high IIP-D in acromegaly. Integrating systematic psychosocial screening into neuroendocrine care, alongside referral to psychoneuroendocrine teams, may help mitigate social disability and improve quality of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068743","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":"Gut Microbiota–Bile Acid–Brain Axis and TGR5-ERK1/2 Signaling Mediate ADT-Induced Cognitive Impairment","authors":"Fan Yang,&nbsp;Yanbo Liu,&nbsp;Zhien Zhou,&nbsp;Dong Yang,&nbsp;Weigang Yan","doi":"10.1111/cns.70608","DOIUrl":"10.1111/cns.70608","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Although a key intervention for advanced Prostate Cancer, Androgen Deprivation Therapy has been associated with cognitive dysfunction, a phenomenon that has been largely attributed to systemic metabolic alterations and neuroinflammation. Nonetheless, the precise role of gut microbiota in ADT-induced cognitive impairment remains unclear, forming the basis of this study. Our aim is to explore the correlation between changes in gut metabolism and cognitive dysfunction following ADT in prostate cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A subcutaneous PC3 tumor-bearing mouse model of ADT-induced cognitive dysfunction was established. Behavioral tests (OFT, NORT, and Y-maze) were conducted to assess cognitive performance. Gut microbiota composition, fecal, and hippocampal bile acid profiles were analyzed by 16S rRNA sequencing and targeted metabolomics. To investigate potential mechanisms, we further supplemented ADT-susceptible (ADT-su) mice with Taurodeoxycholic acid (TDCA) via oral gavage and inhibited ERK1/2 signaling with PD98059, followed by behavioral testing and Western blot analysis of hippocampal Takeda G-protein coupled Receptor 5 (TGR5) and ERK1/2 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hierarchical clustering analysis revealed ADT-induced cognitive impairment in a subset of mice (ADT-susceptible and ADT-unsusceptible). These mice exhibited gut microbiota dysbiosis, featuring the depletion of bile acid-transforming taxa, including <i>Bacteroides</i> spp. and <i>Clostridium scindens</i>. Additionally, FMT from ADT-su mice to pseudo-germ-free mice efficiently transferred cognitive deficits and altered hippocampal bile acid profiles, confirming gut microbiota's causal role in ADT-induced neurocognitive decline. Notably, both gut and hippocampal TDCA levels were significantly decreased in ADT-su mice. Mechanistically, TDCA supplementation improved cognitive performance and upregulated hippocampal TGR5 and p-ERK1/2 expression, while ERK1/2 inhibition by PD98059 partially reversed these effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that gut microbiota-mediated bile acid dysregulation, particularly reduced TDCA, contributes to ADT-induced cognitive dysfunction via impaired TGR5-ERK1/2 signaling. Targeting this pathway may represent a novel therapeutic strategy to mitigate cognitive impairment in prostate cancer patients undergoing ADT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12436682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068768","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":"Thrombolysis to Recanalization Time Affects the Benefit of Bridging Thrombolysis in Large Vessel Occlusion Patients With Successful Recanalization","authors":"Gao-Peng Xing,&nbsp;Wei Li,&nbsp;Chang Cui,&nbsp;Zi-Ai Zhao,&nbsp;Thanh N. Nguyen,&nbsp;Hui-Sheng Chen","doi":"10.1111/cns.70579","DOIUrl":"https://doi.org/10.1111/cns.70579","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Purpose</h3>\u0000 \u0000 <p>The benefit of bridging intravenous thrombolysis (IVT) was conflicting in patients with large vessel occlusion (LVO) who received endovascular treatment (EVT). This study aimed to determine whether IVT to recanalization time (TRT) can affect the benefit of IVT bridging EVT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on a retrospective cohort, eligible LVO patients who achieved successful recanalization after IVT bridging EVT within onset to puncture time of 7 h were enrolled and were divided into TRT ≤ 182 min and TRT &gt; 182 min groups according to median TRT. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). The inverse propensity of treatment weight (IPTW) was used as sensitivity analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 83 eligible patients were enrolled in the final analysis, including 42 in the TRT ≤ 182 min and 41 in the TRT &gt; 182 min group. There was a shift tendency toward a lower degree of functional disability on mRS score at 90 days favoring the TRT ≤ 182 min group compared to the TRT &gt; 182 min group (adjusted OR 1.80, 95% CI 0.69–4.75, <i>p</i> = 0.19), which was confirmed by IPTW analysis (OR 1.73, 95% CI 1.16–2.59, <i>p</i> = 0.06). A numerically higher proportion of excellent functional outcome at 90 days was found in the TRT ≤ 182 min vs. TRT &gt; 182 min group (56.8% vs. 33.8% before IPTW; 58.4% vs. 25.9% after IPTW). There was no difference in sICH between the TRT ≤ 182 min and TRT &gt; 182 min group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Among LVO patients who achieved successful recanalization after IVT bridging EVT, the benefit of IVT may be associated with TRT. This finding needs to be validated in prospective trials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>This trial was registered with ClinicalTrials.gov (NCT04752735)</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70579","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062689","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 Effect on Cortical Reactivity of Theta Burst Versus High-Frequency Repetitive Transcranial Magnetic Stimulation in Parkinson's Disease: A TMS-EEG Study","authors":"Jiajing Wu,&nbsp;Sheng Zhuang,&nbsp;Yinlian Han,&nbsp;Fan Gao,&nbsp;Chengjie Mao,&nbsp;Jing Chen,&nbsp;Chun-feng Liu","doi":"10.1111/cns.70605","DOIUrl":"https://doi.org/10.1111/cns.70605","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Both high-frequency repeated transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) are believed to enhance cortical excitability. However, clinical comparison of their benefits for motor improvement in Parkinson's disease (PD) as well as their underlying neurophysiological changes remain unelucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the clinical effect of rTMS versus iTBS on motor improvement and explore their influence on cortical reactivity using resting state electroencephalogram (EEG) and TMS-EEG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Idiopathic PD patients were randomized in a single-blind, controlled trial, and received 10 sessions of either 10-Hz rTMS or iTBS applied to the bilateral primary motor cortex (M1). Motor symptoms were evaluated using the Unified Parkinson's Disease Rating Scale. Cortical reactivity was assessed by resting state EEG and TMS-evoked potentials.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Included were 52 PD patients (mean [SD] age 66.2 [5.8] years). Compared to 10 Hz rTMS, iTBS was more efficient in alleviating tremor symptoms. In the iTBS group, the global mean field amplitude of P60 was significantly higher after stimulation over contralateral M1 of the affected side and was inversely correlated with motor improvement. In the 10 Hz rTMS group, the global mean field amplitude of P30 evoked by ipsilateral M1 increased significantly. The combination of oscillation and connectivity of <i>δ</i> frequency in the frontal cortex of PD provided a decent model in predicting iTBS responders at baseline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Compared with high-frequency rTMS, iTBS applied to M1 was more effective in improving tremor symptoms in PD. The two non-invasive stimulation modalities appear to exert their effects through distinct neurophysiological pathways, as measured by EEG and TMS-EEG.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70605","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038039","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}