CNS Neuroscience & Therapeutics最新文献

{"title":"Exosomal PSMD1 Derived From Dental Pulp Mesenchymal Stem Cells Promotes Microglial M2 Polarization to Alleviate Spinal Cord Injury","authors":"Xiaohui Xing,&nbsp;Yuan Hao,&nbsp;Guanghui Zhang,&nbsp;Xiaoyang Xing,&nbsp;Hongfei Jia,&nbsp;Chenlong Liu,&nbsp;Xin Wang,&nbsp;Tao Li,&nbsp;Xueyuan Li,&nbsp;Yilei Xiao","doi":"10.1002/cns.71133","DOIUrl":"10.1002/cns.71133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Exosomes derived from mesenchymal stem cells (MSCs) and their cargo contribute to the protective properties of MSCs in spinal cord injury (SCI). This study aimed to explore the role of Proteasome 26S subunit non-ATPase 1 (PSMD1), delivered via exosomes derived from dental pulp mesenchymal stem cells (DPMSCs-Exo), in SCI repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Proteomic profiling was conducted to identify proteins enriched in DPMSCs-Exo. M1/M2 microglial polarization was assessed using flow cytometry, immunofluorescence, and western blotting. The apoptotic rates of BV2 microglia and NE-4C neural stem cells were measured by flow cytometry, whereas cell viability was determined using the CCK-8 assay. Western blotting was performed to analyze proteins involved in autophagy and apoptosis. Pro-inflammatory cytokine levels were quantified using ELISA. Additionally, a mouse SCI model treated with DPMSCs-Exo was established to assess therapeutic effects in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DPMSCs-Exo enriched with PSMD1 suppressed M1-associated inflammatory activation, promoted M2 microglial polarization, and suppressed inflammation in BV2 cells following LPS exposure by activating the JAK2/STAT3 pathway. The shift toward an anti-inflammatory microglial phenotype indirectly enhanced survival, reduced apoptosis, and inhibited autophagy in NE-4C neural stem cells. In SCI mice, exosomal PSMD1 improved locomotor recovery, promoted spinal tissue regeneration at the injury site, reduced inflammation and astrocyte activation, and increased M2 microglial polarization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>DPMSCs-Exo carrying PSMD1 suppressed M1-type inflammatory responses while promoting M2 microglial polarization, thereby attenuating inflammation and astrocyte activation and facilitating SCI repair. These findings suggest that DPMSCs-Exo may be a promising therapeutic candidate for the treatment of SCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":""},"PeriodicalIF":6.6,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13538453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878740","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":"Pyrroloquinoline Quinone Attenuates Traumatic Brain Injury-Induced Secondary Damage by Activating PINK1/Parkin-Mediated Mitophagy and Suppressing ASS1/CPS1-Driven Arginine Biosynthesis.","authors":"Yanan He, Lu Yu, Yixun Lu, Zhikang Zhou, Ao Li, Lu Wang, Zhili Huang, Yanhong Liu, Yulong Ma, Weidong Mi","doi":"10.1002/cns.71146","DOIUrl":"10.1002/cns.71146","url":null,"abstract":"<p><strong>Aims: </strong>Pyrroloquinoline quinone (PQQ) was reported to be neuroprotective after experimental traumatic brain injury (TBI), but its mechanisms remain undefined. We tested whether PQQ protects against TBI in mice and identified the associated pathways.</p><p><strong>Methods: </strong>Male C57BL/6 mice received intraperitoneal PQQ (6.25, 12.5 or 25 mg/kg) immediately after controlled cortical impact. Mortality, modified neurological severity score (mNSS) and beam balance were followed to day 14; histopathology, immunofluorescence, western blot, ELISA and ATP assays were performed on day 3. Transcriptomics, metabolomics, network pharmacology and docking were integrated to identify candidate mechanisms.</p><p><strong>Results: </strong>PQQ reduced mortality (lowest at 12.5 mg/kg) and dose-dependently improved neurological deficits, neuronal apoptosis, brain edema, pro-inflammatory cytokines, and oxidative stress; the mNSS and beam balance benefits persisted to day 14. At 12.5 mg/kg, multi-omics and network pharmacology identified arginine biosynthesis, mediated by argininosuccinate synthetase 1 (ASS1) and carbamoyl phosphate synthetase 1 (CPS1), as the top-ranked pathway suppressed by PQQ; docking predicted binding of PQQ to both enzymes, suggesting putative targets pending validation. PQQ concurrently restored PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy and ATP production.</p><p><strong>Conclusion: </strong>PQQ attenuates secondary injury after TBI in male mice, in association with increased markers of PINK1/Parkin-mediated mitophagy initiation and suppressed ASS1/CPS1-driven arginine biosynthesis, identifying a candidate dual-axis mechanism and nominating the mitophagy-arginine axis as a target for neuroprotection in TBI.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71146"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13559014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917616","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":"Surgery Is Not Associated With Early Presentation of Alzheimer's Disease and Mild Cognitive Impairment or Increased Risk for Both.","authors":"Wenzhe Zang, James Vithoulkas, Zhiyi Zuo","doi":"10.1002/cns.71149","DOIUrl":"10.1002/cns.71149","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most common form of dementia in elderly patients. Mild cognitive impairment (MCI) may be a prodromal status of AD. Previous studies show inconsistent findings on whether surgery increases MCI and AD incidence. Moreover, it remains unknown whether surgery expedites the development of MCI or AD.</p><p><strong>Methods: </strong>This was a retrospective propensity score-matched cohort study using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database between September 2005 (ADNI initiation time) and May 2025 (time of data downloaded). Two outcomes were assessed: age at first diagnosis of MCI or AD, and incidence of MCI or AD. Nearest-neighbor matching was used to balance demographic and comorbidity covariates.</p><p><strong>Results: </strong>The study was composed of 1114 subjects with MCI, 760 subjects with AD, and 397 subjects with normal cognition. Surgery was not associated with a decrease in the age of patients when MCI was diagnosed but was associated with a delayed presentation of AD by 1.7 years. Surgery performed on patients younger than 60 years was associated with a decrease in age when the first diagnosis of MCI or AD was made. Surgery at an age older than 60 years was associated with an increase in the age at MCI or AD diagnosis (mean difference: 5.1 and 5.6 years, respectively). Surgery was not associated with a change in the incidence of MCI or AD.</p><p><strong>Conclusion: </strong>Surgery may be associated with delayed presentation of AD or MCI, except for the surgery performed in patients younger than 60 years. Surgery may not affect the incidence of MCI or AD. These findings do not support deferring clinically indicated surgery for the concern of development of MCI or AD.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71149"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899823","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":"Time-Varying Effective Network of Rehabilitation in Parkinson's Disease With Disease Laterality: A TMS-EEG Study.","authors":"Han Liu, Bo Jiang, Xiao Yang, Mengxuan Hu, Qi Zhu, Keke Chen, Cuiping Xue, Zhaohui Jin, Li Wang, Shintaro Funahashi, Boyan Fang, Guangying Pei, Tianyi Yan","doi":"10.1002/cns.71155","DOIUrl":"10.1002/cns.71155","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is predominantly characterized by unilateral motor manifestations and heterogeneous treatment responses. Combining single-pulse transcranial magnetic stimulation with electroencephalography (TMS-EEG) enables sensitive detection of cortical plasticity and dynamic brain network pathophysiology.</p><p><strong>Methods: </strong>To elucidate the neural mechanisms underlying rehabilitation effects in PD, 27 left-affected (LPD) and 27 right-affected (RPD) patients were enrolled based on concordant lateralization between initial motor-symptom onset and current motor asymmetry quantified from the Movement Disorders Society-Sponsored Revised Unified Parkinson's Disease Rating Scale Part III limb subitems. All participants received a 2-week multidisciplinary intensive rehabilitation therapy (MIRT). By integrating single-pulse TMS-EEG recordings with adaptive directed transfer function analysis, this study evaluated network alterations within the primary motor cortex and posterior parietal cortex before and after MIRT. Furthermore, correlations between neural network changes and clinical functional improvements were examined.</p><p><strong>Results: </strong>Significant alterations in brain network connectivity emerged, most notably 100 ms post-TMS of the posterior parietal cortex in the affected hemisphere. In LPD patients, decreased connectivity from the right central region to the parietal cortex correlated with improvements in axial symptoms, while increased outflow from the bilateral temporal lobes was associated with cognitive enhancement. Conversely, in RPD patients, decreased whole-brain transfer efficiency correlated with improved motor function, and changes in outflow from the left occipital and medial frontal lobes were associated with cognitive enhancement.</p><p><strong>Conclusion: </strong>The distinct modulatory effects of MIRT on the brain networks of LPD and RPD patients provide lateralized mechanistic insights into rehabilitation-related neural mechanisms in PD, potentially guiding the development of personalized and optimized therapeutic strategies.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71155"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981731","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":"Temporal Mapping of CSVD-Related White Matter Lesions and Concurrent Neurovascular Dysfunction in Spontaneously Hypertensive Rats.","authors":"Jing Peng, Jingnian Ni, Fuyao Li, Ting Li, Mingqing Wei, Tianci Ge, Lulu Yao, Jing Shi, Jinzhou Tian","doi":"10.1002/cns.71142","DOIUrl":"10.1002/cns.71142","url":null,"abstract":"<p><strong>Objective: </strong>To define the critical onset window and mechanisms of white matter lesions (WMLs) in cerebral small vessel disease based on spontaneously hypertensive rat (SHR).</p><p><strong>Methods: </strong>SHRs and age-matched Wistar-Kyoto (WKY) rats were assessed from 20 to 36 weeks of age. Systolic blood pressure, beam-walking performance, and magnetic resonance imaging (MRI)-based white matter changes were evaluated at 4-week intervals. At each time point, randomly selected animals were euthanized for histological analysis. Gait performance and novel object recognition were further assessed at 36 weeks of age. Additional histopathological, neurovascular, neuroinflammatory, transcriptomic, proteomic, and biochemical analyses were performed at the identified critical time point.</p><p><strong>Results: </strong>SHRs developed sustained hypertension and early small-vessel morphological alterations from 20 weeks, followed by corpus callosum demyelination at 28 weeks and motor, gait, and non-spatial memory deficits by 36 weeks. MRI identified 28 weeks as the onset of detectable white matter microstructural impairment, marked by reduced fractional anisotropy, axial diffusivity, and increased radial diffusivity. At this stage, histological and molecular analyses confirmed myelin disruption, altered mature oligodendrocyte (OL)- and oligodendrocyte precursor cell (OPC)-associated marker profiles, microvascular rarefaction, blood-brain barrier disruption, and inflammation in SHRs. Transcriptomic analysis highlighted cAMP pathway dysregulation, whereas proteomic analysis identified Pde10a as a significantly upregulated candidate protein. Suppression of downstream cAMP/PKA/CREB signaling was further supported by biochemical validation.</p><p><strong>Conclusions: </strong>WMLs emerge at 28 weeks in SHRs and are accompanied by convergent neurovascular injury and inflammatory activation. Pde10a-associated cAMP signaling may represent a candidate mechanism associated with hypertension-related WML development in CSVD.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71142"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928508","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":"Ganoderic Acid A Ameliorates Pentylenetetrazol-Induced Epilepsy in Mice via Activating KCNQ2.","authors":"Yang Yao, Zhujun Liu, Xujiao Wang, Cunhao Bian, Rui Wang, Yukun Zhang","doi":"10.1002/cns.71152","DOIUrl":"10.1002/cns.71152","url":null,"abstract":"<p><strong>Trial design: </strong>This study aimed to explore the antiepileptic effect of Ganoderic acid A (GA-A) on pentylenetetrazol (PTZ)-induced epilepsy in mice and clarify its underlying mechanism, focusing on the KCNQ2 channel.</p><p><strong>Methods: </strong>C57BL/6 mice and hippocampal-specific KCNQ2 knockout mice were used to establish PTZ-induced acute epilepsy models. GA-A was pretreated for 7 days. Epileptic seizures were evaluated by the Racine score and electroencephalogram (EEG). Neuronal injury was detected by HE and TUNEL staining. Neuroinflammation and oxidative stress were assessed by measuring inflammatory factors and oxidative markers. The target interaction between GA-A and KCNQ2 was verified by protein chip, molecular docking, surface plasmon resonance (SPR), and electrophysiological recording.</p><p><strong>Results: </strong>GA-A dose-dependently reduced seizure severity, shortened epileptiform discharge duration, alleviated hippocampal neuronal loss and apoptosis, and inhibited neuroinflammation and oxidative stress in PTZ-treated mice. GA-A directly bound to KCNQ2 and activated KCNQ2/3 channels to generate M current. Hippocampal KCNQ2 knockout weakened the ameliorative effect of GA-A on EEG abnormalities and epilepsy-related anxiety- and depression-like behaviors, but did not affect its anti-inflammatory and antioxidant effects.</p><p><strong>Conclusion: </strong>GA-A attenuates PTZ-induced epilepsy in mice via activating the KCNQ2 channel to suppress neuronal hyperexcitability and independently inhibiting neuroinflammation and oxidative stress. GA-A is a promising KCNQ2 activator and lead compound for antiepileptic drug development.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71152"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035891","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":"PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.","authors":"Jing Zhang, Peng Wang, Nan Li, Yan Gao","doi":"10.1002/cns.71103","DOIUrl":"10.1002/cns.71103","url":null,"abstract":"<p><strong>Objective: </strong>To assess whether pioglitazone (Pio) protects against sepsis-associated encephalopathy (SAE) and to probe underlying mechanisms.</p><p><strong>Methods: </strong>Sepsis was induced in male C57BL/6 mice by caecal ligation and puncture (CLP). At 24 h post-CLP, mice received Pio and/or the PPAR-γ antagonist GW9662 and were followed for 14-day survival. Cognitive and affective behaviors were evaluated using a behavioral battery. Blood-brain barrier (BBB) permeability was assessed by Evans blue extravasation, and hippocampal inflammatory and apoptotic readouts were examined by ELISA, immunoblotting, and TUNEL staining.</p><p><strong>Results: </strong>CLP reduced 14-day survival to 21.82%, whereas Pio increased survival to 46.15%; GW9662 abolished this benefit (19.36%). Pio improved behavior consistent with reduced anxiety-like behavior and better learning/memory. Mechanistically, Pio decreased Evans blue leakage and increased Claudin-5, suppressed TLR4/NF-κB-associated inflammation (lower TNF-α, IL-1β, and IL-6; higher IL-10), and reduced neuronal apoptosis; these effects were largely reversed by GW9662.</p><p><strong>Conclusion: </strong>Pioglitazone alleviates sepsis-induced brain dysfunction and improves survival in mice in a PPAR-γ-dependent manner.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71103"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862855","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":"Accelerated Intermittent Theta-Burst Stimulation for the Treatment of Alcohol Use Disorder: A Randomized Sham-Controlled Study With Six-Month Follow-Up.","authors":"Yunsheng Hou, Jingying Zhang, Shiyun Wang, Kunya Liu, Bingyu Zhang, Hongdu Deng, Rongrong Wang, Ying Xu, Dan Wang, Chuansheng Wang, Tianzhen Chen, Ruiling Zhang","doi":"10.1002/cns.71166","DOIUrl":"10.1002/cns.71166","url":null,"abstract":"<p><strong>Background: </strong>Accelerated intermittent theta-burst stimulation (a-iTBS) is a novel rTMS protocol increasingly used for mental disorders, but its application in alcohol use disorder (AUD) remains early. This exploratory sham-controlled study evaluated a 50-session a-iTBS protocol for AUD.</p><p><strong>Methods: </strong>Sixty-one male AUD inpatients were randomized to receive traditional iTBS (once daily, 600 pulse/session), a-iTBS (5 sessions/day, 3000 pulses/day), or sham iTBS. Treatments were administered on 10 weekdays (Monday to Friday over 2 weeks) and targeted the dorsolateral prefrontal cortex. The primary outcome was the change in craving. The alcohol relapse behavior, emotional symptoms, and sleep quality were evaluated pre-/post-intervention.</p><p><strong>Results: </strong>Group showed no significant main effect on craving percentage change. The a-iTBS group showed a higher response rate and earlier response onset than the s-iTBS group, whereas no significant differences existed between a-iTBS and iTBS, or iTBS and s-iTBS. No intergroup differences were detected for mood and sleep indicators. At the 6-month follow-up, participants receiving a-iTBS achieved longer abstinence duration than those given s-iTBS. Exploratory logistic regression indicated that baseline GAD-7 scores and treatment group were associated with treatment response.</p><p><strong>Conclusions: </strong>Although the primary craving outcome did not differ significantly among groups, a-iTBS showed preliminary signals of earlier response and longer time to first relapse than sham stimulation. These exploratory findings require confirmation in larger trials.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71166"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975112","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":"Whole-Brain Monosynaptic Inputs to and Axonal Projections From Posterior Insular Cortex GABAergic Neurons in Mice.","authors":"Wan-Qiao Qi, Xin-Yue Zhang, Wei-Xiang Ma, Wei-Min Qu, Jia-Qi Shi, Zhi-Li Huang, Yu-Lan Zhu","doi":"10.1002/cns.71102","DOIUrl":"10.1002/cns.71102","url":null,"abstract":"<p><strong>Background: </strong>The posterior insular cortex (PIC) is a multimodal sensory integration center, and the GABAergic neurons are associated with functions such as pain perception, emotional regulation, and fear memories encoding. However, the whole-brain connectivity to PIC GABAergic neurons remains unclear.</p><p><strong>Objective: </strong>To map the whole-brain input-output connectivity of PIC GABAergic neurons.</p><p><strong>Methods: </strong>This study combined cell-type-specific retrograde/anterograde viral tracing systems with Cre/loxP genetic technology to perform a comparative analysis of the localization and quantification of monosynaptic inputs and axonal projections of PIC GABAergic neurons.</p><p><strong>Results: </strong>Retrograde tracing identified 45 input nuclei, with densest inputs from the piriform cortex (Pir) and secondary somatosensory cortex (S2) of the isocortex, thalamic nuclei including the posterior thalamic nuclear group (PO) and parafascicular thalamic (PAF), exhibiting ipsilateral preference. Anterograde tracing revealed 18 output targets, with densest projections to the caudate putamen (CPu), external globus pallidus (GPe), and ventral pallidum (VP) of the basal ganglia and multiple subnuclei of the amygdala.</p><p><strong>Conclusions: </strong>PIC GABAergic neurons receive dense inputs from the isocortex and thalamus and send prominent projections to the basal ganglia and amygdala, with these brain regions constituting key hubs of the whole-brain connectivity network. This connectivity pattern provides a novel anatomical perspective for elucidating their roles in physiological behavior regulation.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71102"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890580","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":"Cannabidiol Ameliorates Blood-Brain Barrier Dysfunction and Inhibits Memory Astrocytes Activation in Mice With Sickness-Like Behaviors.","authors":"Yue Chen, Hui Ma, Qian Long, Xuan Fang, Xiaotong Li, Wenhui Xiao, Xinzhou Deng, Fuze Du, Yifei Tan, Yan Wang, Xiaoxia Jiang, Bo Gao, Xin Qiao","doi":"10.1002/cns.71168","DOIUrl":"10.1002/cns.71168","url":null,"abstract":"<p><strong>Background: </strong>Blood-brain barrier (BBB) dysfunction has been increasingly implicated in the pathophysiology of depression; however, effective therapeutic strategies targeting this pathology remain limited. This study aimed to investigate the effect of cannabidiol (CBD) on improving depressive-like behaviors and BBB impairment, as well as its underlying mechanism.</p><p><strong>Methods: </strong>Depressive-like behaviors in mice were assessed via exploratory and despair-like tests. BBB integrity was evaluated by examining tight junction protein expression in endothelial cells and AQP4 reduction from the perivascular membrane. Astrocyte activation and neuroinflammation were also measured. The therapeutic effects of a single CBD dose were examined.</p><p><strong>Results: </strong>Mice with depressive-like phenotypes showed reduced exploratory behavior and increased despair-like behavior. In the BBB, the expression of tight junction proteins in endothelial cells was downregulated; in astrocytes, decreased AQP4 expression was observed, abnormal activation was enhanced, and neuroinflammation was elevated. A single dose of CBD alleviated all the above pathological changes. Further studies demonstrated that CBD exerted its effects by inhibiting memory astrocyte-associated secondary neuroinflammation, thereby alleviating depressive-like behaviors in mice with depressive-like phenotypes.</p><p><strong>Conclusion: </strong>Experimental results show that CBD treatment can improve BBB dysfunction in depression and further indicates that targeted inhibition of memory astrocytes-mediated neuroinflammation may promote the treatment of depression.</p>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"32 9","pages":"e71168"},"PeriodicalIF":6.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975162","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}