CNS Neuroscience & Therapeutics最新文献

{"title":"Targeting Microglial HDAC5 Suppresses NLRP3 Inflammation via NF-κB Deacetylation to Alleviate Ischemic Brain Injury.","authors":"Ru-Yu Liang, Jia-Qi Zhang, Tian-Yi Jiang, Li-Qing Tao, Wen She, Zhou-Na Sun, Cui Qi, Jun Gao","doi":"10.1002/cns.71161","DOIUrl":"10.1002/cns.71161","url":null,"abstract":"<p><strong>Objective: </strong>Histone deacetylases are implicated in ischemic stroke, yet the role of HDAC5 remains poorly defined. This study aimed to determine the pathological significance of HDAC5 after cerebral ischemia, clarify its involvement in post-ischemic NF-κB p65/NLRP3 signaling, and evaluate an HDAC5-targeted extracellular vesicle (EV)-based therapeutic strategy.</p><p><strong>Methods: </strong>HDAC5 expression after ischemic injury was examined in a mouse middle cerebral artery occlusion (MCAO) model by western blotting and immunofluorescence. Its function was assessed by gain- and loss-of-function experiments in BV2 cells and MCAO mice. Infarct volume, cerebral blood flow, and neurological recovery were evaluated by TTC staining, magnetic resonance imaging (MRI), color Doppler imaging, and behavioral tests. Co-immunoprecipitation, acetylation analysis, and cytoplasmic/nuclear fractionation were used to explore the underlying mechanism. Human neural stem cell-derived EVs loaded with miR-9-5p and modified with RGD peptide were further tested as a targeted therapeutic approach.</p><p><strong>Results: </strong>HDAC5 was markedly upregulated after MCAO, localizing mainly to neurons in the ischemic core and microglia in the penumbra, together with increased NLRP3 expression. In BV2 cells, HDAC5 overexpression increased NLRP3 expression, whereas HDAC5 knockdown reduced it. In vivo, AAV-mediated HDAC5 knockdown decreased NLRP3 levels, reduced infarct volume, improved blood flow recovery, and ameliorated motor deficits after MCAO. Mechanistically, HDAC5 interacted with NF-κB p65 rather than NLRP3. HDAC5 knockdown increased p65 acetylation and reduced its nuclear translocation, consistent with suppression of NLRP3-associated inflammatory signaling. Moreover, engineered RGD-EV:miR-9-5p was efficiently taken up by microglia, suppressed HDAC5 and NLRP3 expression, and improved histological and functional outcomes after MCAO.</p><p><strong>Conclusion: </strong>These findings identify HDAC5 as a previously underappreciated regulator of post-ischemic inflammatory injury and support a role for the HDAC5/NF-κB p65/NLRP3 axis in cerebral ischemia. Engineered RGD-EV:miR-9-5p may therefore represent a promising targeted therapeutic strategy for ischemic stroke.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71161"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13624526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079093","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":"Shared Genetic Architecture Between Common Epilepsies and Subcortical Brain Volumes Is Associated With Cognition and Mental Health.","authors":"Zesheng Li, Qian Wu, Yanfeng Yang, Jianwei Shi, Xuegang Niu, Yuanyuan Zhang, Yumin Luo, Cheng Wei, Yongzhi Shan, Feng Liu, Josemir W Sander, Guoguang Zhao","doi":"10.1002/cns.71156","DOIUrl":"https://doi.org/10.1002/cns.71156","url":null,"abstract":"<p><strong>Aims: </strong>Epilepsy is a common neurological disorder, often presenting with psychiatric comorbidities and cognitive impairment. Neuroimaging studies have suggested associations between epilepsy and subcortical volumetric abnormalities. The genetic basis between epilepsy and subcortical volume abnormalities is, however, poorly understood, particularly if they share a common genetic architecture.</p><p><strong>Methods: </strong>To investigate polygenic overlap, we employed the bivariate causal mixture model (MiXeR) to analyze genome-wide association data from various epilepsy subtypes (genetic generalized epilepsy [GGE]: n = 49,388, all epilepsy [EP]: n = 69,995, focal epilepsy: n = 57,375) and 16 subcortical volumetric phenotypes (n = 33,224). We identified shared genomic loci through conditional and conjunctional false discovery rate analyses (cond/conjFDR).</p><p><strong>Results: </strong>MiXeR results suggest substantial shared genetic variants between subcortical volume and common epilepsies. ConjFDR analysis identified 33 distinct shared loci between GGE and subcortical volumetric phenotypes. The shared loci were mapped to 322 protein-coding genes. Among these, 49 genes showed significant expression-trait associations with both GGE and subcortical volume phenotypes, and 12 of the 322 genes were also associated with cognitive, mental health, and personality-related traits.</p><p><strong>Conclusion: </strong>We dissected the shared genetic architecture between common epilepsies and subcortical volumes. Expression-trait association analyses further identified candidate genes associated with cognitive, mental health, and personality-related phenotypes.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71156"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101544","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 Role of Glymphatic Clearance in Affective Decision-Making in Adolescents with Non-Suicidal Self-Injury.","authors":"Hongping Wang, Jiahua Zhang, Ruizi Pan, Xiaoqian Ye, Rong Wang, Ke Lv, Yue Yu, Qianqian Li, Ting Zhang, Dongpeng Wu, Dai Zhang, Yanghua Tian","doi":"10.1002/cns.71159","DOIUrl":"https://doi.org/10.1002/cns.71159","url":null,"abstract":"<p><strong>Background: </strong>Adolescents with non-suicidal self-injury (NSSI) frequently exhibit severe sleep disturbances and heterogeneous cognitive impairments, yet the underlying neurophysiological basis remains unclear. The glymphatic system, a sleep-dependent macroscopic clearance network, is critical for metabolic waste removal and neurocognitive homeostasis. Therefore, this study aimed to investigate the physiological role of glymphatic function in linking sleep burden to distinct cognitive performances in adolescents with NSSI.</p><p><strong>Methods: </strong>We assessed 44 NSSI adolescents and 33 healthy controls (HCs). Using resting-state functional magnetic resonance imaging (rs-fMRI), glymphatic function was quantified by calculating the coupling strength between global blood-oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) flow. To capture the heterogeneity in their cognitive profiles, we evaluated \"hot\" affective decision-making via the Iowa Gambling Task (IGT) and \"cold\" executive function via the Wisconsin Card Sorting Test (WCST). Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI).</p><p><strong>Results: </strong>In the NSSI group, poorer sleep quality was positively correlated with stronger gBOLD-CSF coupling (r = 0.317, p = 0.036), and stronger gBOLD-CSF coupling predicted better IGT performance, especially during the high-load strategy phase (Block 3) (r = 0.447, p = 0.002). Furthermore, glymphatic function fully mediated the relationship between sleep quality and affective decision-making performance (indirect effect = 0.682, 95% CI [0.062, 1.515]). Interaction analyses confirmed this physiological-behavioral coupling was disease-specific (present only in NSSI; interaction p = 0.011) and domain-specific (supporting \"hot\" affective cognition rather than \"cold\" executive function).</p><p><strong>Conclusions: </strong>In NSSI adolescents, sleep-associated glymphatic upregulation reflects a stress-induced compensatory response. This mechanism domain-specifically preserves high-load affective decision-making against severe psychopathological stress. These findings highlight brain metabolic clearance as a novel physiological target for bolstering cognitive resilience in high-risk youth.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71159"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101658","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":"Ictal Epileptogenic Network Differences in Posterior Cingulate Epilepsy Subtypes Based on SEEG","authors":"Zhaofen Yan,&nbsp;Yujiao Yang,&nbsp;Jing Wang,&nbsp;Qin Qin Deng,&nbsp;Minghui Wang,&nbsp;Huajun Yang,&nbsp;Jiali Pan,&nbsp;Jian Zhou,&nbsp;YuGuang Guan,&nbsp;Guoming Luan,&nbsp;Mengyang Wang","doi":"10.1002/cns.71192","DOIUrl":"10.1002/cns.71192","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To compare differences in ictal propagation between epileptogenic networks between posterior cingulate cortex (PCC) epilepsy and retrosplenial cortex (RSC) epilepsy and to elucidate their network-level pathophysiological characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 18 patients with confirmed PCC or RSC-related epilepsy were enrolled in this study. We calculated directed functional connectivity across preictal, ictal onset, and propagation phases based on pairwise nonlinear regression (<i>h</i>² coefficient). Using graph theory and linear mixed-effects models, we quantified network topology and dynamic propagation patterns of epileptogenic networks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Neuropsychological tests showed significantly poorer visual recall in patients with RSC epilepsy (<i>p</i> = 0.030). During the propagation phase, the ipsilateral mesial temporal structures showed significantly greater node out-strength than in-strength, acting as a secondary driver of seizure spread (<i>p</i> = 0.004). The lateral temporal cortex acted as a signal receiver with dominant in-strength (<i>p</i> = 0.015). RSC epilepsy also showed stronger directional propagation toward ipsilateral mesial temporal areas than PCC epilepsy (<i>p</i> = 0.022), whereas PCC epilepsy lacked consistent directional connectivity across key regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>RSC and PCC epilepsy display inherent differences in visuospatial memory performance and ictal network dynamics. The preferential propagation toward ipsilateral mesial temporal structures in RSC epilepsy may represent a potential electrophysiological correlate for distinguishing posterior cingulate epilepsy subtypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101608","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":"Inhibition of Cerebellar Dentate Nucleus-Zona Incerta Glutamatergic Circuit Improves Sleep Disturbances in Chronic Temporal Lobe Epilepsy Model.","authors":"Liang Xia, Xuan Wang, Yingchi Zhang, Jianmin Hao, Dan Mi, Changgeng Song, Wen Jiang","doi":"10.1002/cns.71207","DOIUrl":"10.1002/cns.71207","url":null,"abstract":"<p><strong>Background: </strong>Patients with chronic temporal lobe epilepsy (TLE) frequently experience various sleep disorders, characterized by reduced sleep duration, diminished sleep stages, and disrupted sleep patterns. Recent research has identified a population of GABAergic neurons in the ventral zona incerta (ZI) that is instrumental in promoting sleep, along with a neural pathway that connects the cerebellar dentate nucleus (CDN) to the ZI. However, the precise role of this circuit in regulating sleep patterns remains inadequately understood.</p><p><strong>Methods: </strong>This study employed anatomical, chemogenetic, optogenetic, and immunofluorescence staining techniques to investigate the potential of the CDN-ZI circuit in ameliorating sleep disturbances associated with TLE.</p><p><strong>Results: </strong>Our findings indicate that pilocarpine-treated mice exhibit significant sleep fragmentation and reduced sleep duration, particularly during non-rapid eye movement sleep. By employing optogenetic and chemogenetic methods to target CDN glutamatergic neurons, we observed a decrease in sleep fragmentation, an increase in overall sleep duration, and an enhancement in sleep quality in pilocarpine-treated mice. The inhibition of the CDN-ZI glutamatergic circuit through optogenetic and chemogenetic methods resulted in substantial improvements in sleep disturbances following TLE.</p><p><strong>Conclusions: </strong>Targeting the CDN-ZI glutamatergic circuit represents a promising therapeutic strategy for addressing sleep disorders resulting from chronic TLE.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71207"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178313","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 Ameliorates Alcohol-Related Cognitive Impairment by Modulating the Gut-Brain Axis to Alleviate LPS Driven Neuroinflammation.","authors":"Yueqin Liu, Jianjie Luo, Shuyou Wang, Yinwen Wu, Shuyong Jia, Guangjun Wang, Weiguo Xue, Xiaojing Song","doi":"10.1002/cns.71213","DOIUrl":"10.1002/cns.71213","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether electroacupuncture (EA) at Zusanli (ST36) ameliorates alcohol-related cognitive impairment (ARCI) by restoring intestinal barrier integrity and to elucidate the role of the vagus nerve in this \"gut-to-brain\" protective mechanism.</p><p><strong>Methods: </strong>An ARCI mouse model was established by daily ethanol gavage for 28 days. Mice received EA at ST36 from day 15 onwards. Behavioral tests (MWM, OFT, EPM) were conducted to assess cognitive and emotional function. Time-course analysis of intestinal pathology (H&E, ZO-1), permeability (FITC-LPS, DAO), and neuroinflammation (LPS, IBA-1, cytokines) was performed. The role of the vagus nerve was investigated using ipsilateral DMV lesion and exogenous LPS challenge.</p><p><strong>Results: </strong>Chronic alcohol exposure caused significant cognitive deficits, anxiety-like behaviors, and body weight loss, accompanied by early-onset intestinal barrier disruption and elevated LPS, which preceded central neuroinflammation. EA at ST36 significantly ameliorated these behavioral and pathological changes. EA activated DMV cholinergic neurons, restored ZO-1 expression, and reduced LPS translocation. Crucially, both DMV lesion and exogenous LPS administration abolished EA's protective effects on the intestinal barrier, neuroinflammation, and behavior.</p><p><strong>Conclusion: </strong>EA at ST36 alleviates ARCI by activating the vagus nerve to restore intestinal barrier integrity, thereby preventing gut-derived LPS from triggering neuroinflammation. This identifies a key vagal-dependent mechanism and supports EA as a promising intervention for ARCI.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71213"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206369","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":"Brain-Wide Connectivity and Topographic Organization of Leptin Receptor Neurons in the Dorsomedial Hypothalamus","authors":"Yaxin Hao,&nbsp;Xiang Zhang,&nbsp;Danyang Zhao,&nbsp;Haixing Zhong,&nbsp;Yongqiang Chen,&nbsp;Heming Li,&nbsp;Minghui Ren,&nbsp;Mengchu Zhu,&nbsp;Fang Yuan","doi":"10.1002/cns.71185","DOIUrl":"10.1002/cns.71185","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The dorsomedial hypothalamus (DMH) integrates metabolism and autonomic homeostasis, but whether subnuclear functional topography exists remains unclear. This study compared whole-brain input–output connectomes of leptin receptor (LepRb) neurons in dorsal DMH (DMD) versus DMH to test for connection-biased segregation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rabies monosynaptic retrograde tracing and Cre-dependent AAV anterograde tracing in LepRb-Cre mice mapped and quantified input–output projections of DMD^LepRb and DMH^LepRb neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both DMD^LepRb and DMH^LepRb neurons received inputs from 58 upstream nuclei and projected to 43 downstream targets across the telencephalon, diencephalon, midbrain, pons, and medulla, forming extensive overlapping networks with similar global architectures. Nevertheless, they showed significant connection weight biases: DMD^LepRb preferentially integrated arousal, defensive, and emotional signals and projected to stress/defense-related nuclei, whereas DMH^LepRb preferentially integrated viscerosensory and reward-aversion signals and projected to metabolic/circadian nuclei.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DMD^LepRb and DMH^LepRb neurons share highly homologous whole-brain input–output architecture but exhibit local connection-weight biases, revealing conserved architecture with local specialization and providing a circuit basis for functional heterogeneity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101536","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":"Sex-Specific Effects of Dexmedetomidine on Brain Microvascular Endothelial Cell Function After Traumatic Brain Injury in Juvenile Mice.","authors":"Yara Mashal, Jie Fan, Tia Atoui, Zahrah Naseer, Sara Moughni, Iman Tawil, Zhi Zhang","doi":"10.1002/cns.71204","DOIUrl":"10.1002/cns.71204","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to evaluate the effects of dexmedetomidine (DEX), a selective α2-adrenergic receptor agonist, on brain microvascular endothelial cell (BMEC) function and blood-brain barrier (BBB) integrity in juvenile mice following traumatic brain injury (TBI). We specifically assessed the effects of DEX on ER stress, neuroinflammation, and ferroptosis and explored potential sex-specific responses.</p><p><strong>Methods: </strong>Male and female juvenile mice were subjected to an impact-acceleration TBI model. DEX was administered during the acute phase post-injury. Muscle strength and sensorimotor coordination were measured, and BBB permeability was assessed. BMECs and cerebral microvessels were isolated from the injured and control regions for molecular analysis of inflammatory markers, ER stress activation, ferroptosis, and expression of tight junction markers.</p><p><strong>Results: </strong>DEX treatment improved motor and coordination outcomes and reduced BBB leakage in both sexes after TBI. Molecular analyses revealed decreased inflammatory signaling, ER stress, and ferroptosis-related oxidative stress pathways in BMECs with DEX treatment. Importantly, DEX led to greater upregulation of selected tight junction markers in female mice than in male mice, suggesting possible sex-specific differences in α2-adrenergic receptor expression.</p><p><strong>Conclusion: </strong>DEX provides both behavioral and cellular protection following juvenile TBI, with potential sex-dependent effects on BMECs and BBB function.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":"e71204"},"PeriodicalIF":6.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163330","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":"Magnetic Resonance Imaging in Cerebral Small Vessel Disease-Related Depression: From Visual Scoring to Artificial Intelligence","authors":"Chaofang Lei,&nbsp;Jiaxu Chen,&nbsp;Yilong Wang","doi":"10.1002/cns.71188","DOIUrl":"10.1002/cns.71188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cerebral small vessel disease (CSVD) is the key pathological basis of vascular depression. The precise identification of its neuroimaging markers is of core value for early diagnosis, elucidation of its pathological mechanism, and individualized treatment. Recent advances in magnetic resonance imaging (MRI) and artificial intelligence (AI) have enabled automated, high-throughput characterization of CSVD-related brain lesions. However, the translation of these technical advances into clinical tools for depression-specific prediction and classification remains at an early stage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>This manuscript aims to summarize the application of traditional visual scoring systems in assessing the burden of CSVD and its association with depressive symptoms. Review the current status of imaging and AI research on CSVD-related depression. To provide a direction for the development of more precise and efficient imaging diagnostic tools for the future, and ultimately promote the practical application and utilization of precision medicine in the field of CSVD-related depression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101565","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":"Modulation of Endoplasmic Reticulum Stress via CEBPB: A Potential Molecular Link to Therapeutic Action in Substance Use Disorders","authors":"Cheng Zhang,&nbsp;Hu Li,&nbsp;Ming-Fen Ho","doi":"10.1002/cns.71183","DOIUrl":"https://doi.org/10.1002/cns.71183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Opioid use disorder remains a major public health crisis in the United States, driven largely by rising overdose deaths from synthetic opioids, such as fentanyl. Emerging population-level evidence suggests that GLP-1 receptor agonists (GLP-1RAs) may reduce overdose risk. However, their underlying molecular mechanisms are not well understood. We investigated the transcriptional effects of fentanyl and GLP-1RAs using human induced pluripotent stem cell (iPSC)-derived forebrain organoids and neurons.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Organoids were treated with fentanyl, liraglutide, or exenatide, followed by RNA sequencing. We extended these analyses to iPSC-derived neurons exposed to additional therapeutic candidates, including the anticonvulsants topiramate and gabapentin, and the metabolic modulator β-hydroxybutyrate. All compounds were tested at clinically relevant concentrations, and transcriptomic and functional genomic assays were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Across models and drug classes, we identified modulation of endoplasmic reticulum (ER) stress signaling as a shared molecular mechanism. Fentanyl and GLP-1RAs consistently downregulated ER stress-related genes, with TRIB3 as the most strongly suppressed target. We further identified CEBPB as a key upstream regulator and confirmed reduced CEBPB DNA-binding activity in ER stress-related genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight ER stress modulation as a convergent pathway with potential therapeutic relevance for substance use disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 10","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cns.71183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068466","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}