Neuroreport最新文献

{"title":"Paeonol mitigates chronic stress-induced amygdalar neuronal damage through glycogen synthase kinase-3β/calcineurin axis regulation of synaptic plasticity.","authors":"Qiang Li, Xili Yan, Yingdi Zhao, Zhiliang Xu, Xiuling Zhu","doi":"10.1097/WNR.0000000000002188","DOIUrl":"https://doi.org/10.1097/WNR.0000000000002188","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to elucidate the neuroprotective mechanisms of paeonol in ameliorating chronic stress-induced amygdala neuronal injury via modulation of the glycogen synthase kinase-3β (GSK3β)/calcineurin signaling pathway. Paeonol, a polyphenolic compound from Moutan Cortex, exhibits therapeutic effects. Studies show it alleviates lipopolysaccharide-induced depression-like behaviors in mice, though its mechanisms remain unclear.</p><p><strong>Methods: </strong>Forty-eight Sprague-Dawley rats were divided into four groups: control, chronic unpredictable mild stress (CUMS) model, low-dose paeonol (25 mg/kg), and high-dose paeonol (80 mg/kg). Paeonol was administered intragastrically 1-week post-CUMS induction for 4 weeks. Behavioral tests assessed depression-like behaviors. Neuronal morphology was evaluated via hematoxylin and eosin, Nissl, and Golgi staining, while western blot quantified cofilin1, p-cofilin1, GSK3β, and calcineurin expression.</p><p><strong>Results: </strong>CUMS rats exhibited depressive-like behaviors, neuronal nuclear pyknosis, interstitial edema, hyperchromatic cytoplasm, and reduced Nissl body integrity. Golgi staining revealed increased dendritic complexity and spine density. CUMS upregulated p-cofilin1 and GSK3β while downregulating total cofilin1 and calcineurin. Paeonol treatment alleviated depressive behaviors, reduced neuronal damage, and normalized dendritic complexity and spine density. Molecularly, paeonol suppressed p-cofilin1 and GSK3β expression while restoring cofilin1 and calcineurin levels.</p><p><strong>Conclusion: </strong>Chronic stress induces dendritic hypertrophy and spine hyperplasticity, contributing to depressive phenotypes. Paeonol counteracts these effects, likely by modulating the GSK3β/calcineurin pathway, highlighting its therapeutic potential for stress-related neuronal injury.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous administration of mesenchymal stem cell-derived exosomes mitigates traumatic brain injury by inhibiting neutrophil extracellular trap formation via miR-26a-5p.","authors":"Yichao Ye, Xiaoxiang Hou, Xianzheng Sang, Hantong Shi, Yangu Guo, Chengzi Yang, Wen Chen, Hanzi Cai, Chaogui Peng, Yunqing Li, Shi Yu, Danfeng Zhang, Lijun Hou","doi":"10.1097/WNR.0000000000002187","DOIUrl":"https://doi.org/10.1097/WNR.0000000000002187","url":null,"abstract":"<p><strong>Objective: </strong>Traumatic brain injury (TBI) results in severe long-term sequelae. While mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated the ability to regulate microglial responses and neuroinflammation, their impact on neutrophil inactivation, particularly in relation to neutrophil extracellular traps (NETs), has not yet been fully elucidated. This research was designed to explore the potential involvement of MSC-Exos in modulating NET formation and microglial polarization following TBI.</p><p><strong>Methods: </strong>A murine TBI model and an in-vitro lipopolysaccharide-induced microglial activation model were utilized to evaluate the effects of miR-26a-5p-enriched exosomes on NET inhibition, microglial polarization, reduction of neuroinflammation, and promotion of neural function recovery.</p><p><strong>Results: </strong>Treatment with MSC-Exos post-TBI reduced NET formation and decreased microglial polarization into a proinflammatory phenotype. Genome-wide prediction detected miR-26a-5p as a predominant component of MSC-Exos, which was closely associated with TAB2. Functional assays demonstrated that miR-26a-5p suppressed NET formation in neutrophils and modulated microglial polarization. MRI and histopathological assessments confirmed that MSC-Exos enriched with miR-26a-5p significantly reduced neuronal death and lesion volume. Moreover, miR-26a-5p was found to regulate microglial polarization and reduce neuroinflammation via the TAB2/JNK/AP1 signaling pathway. Cognitive assessments employing the Morris Water Maze and Modified Neurological Severity Scores revealed significant improvements in neural function following treatment.</p><p><strong>Conclusion: </strong>These findings underscore the potential of MSC-Exos-miR-26a-5p to inhibit NET formation, modulate microglial polarization toward an anti-inflammatory phenotype, and enhance recovery from neural damage in TBI through the TAB2/JNK/AP1 pathway.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Similarities and differences in the cognitive control roles of inferior frontal gyrus and dorsolateral prefrontal cortex in the creative process: a transcranial direct current stimulation study.","authors":"Ying Li, Man Zhang, Yan Chen, Yuntian Xie, Songqing Li, Quanlei Yu, Qingbai Zhao","doi":"10.1097/WNR.0000000000002185","DOIUrl":"https://doi.org/10.1097/WNR.0000000000002185","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that two core subregions of the prefrontal cortex - the dorsolateral prefrontal cortex (DLPFC) and the inferior frontal gyrus (IFG) - are both closely related to cognitive control in creativity; however, the similarities and differences in their cognitive control mechanisms during creativity remain to be further clarified.</p><p><strong>Methods: </strong>This study employed a within-subject design, using transcranial direct current stimulation to manipulate the activity of left DLPFC and IFG separately. Participants completed divergent and convergent thinking tasks under three conditions: anodal stimulation of the left DLPFC, cathodal stimulation of the left IFG, and sham stimulation. The novelty and appropriateness of generated answers during idea generation, as well as those selected during idea selection, were compared across conditions.</p><p><strong>Results: </strong>(a) Anodal stimulation of the left DLPFC significantly enhanced the novelty of answers generated during idea generation in both the alternate uses task (AUT) and the product improvement task and helped to select the more appropriate answer during idea selection in AUT. (b) Cathodal stimulation of the left IFG significantly improved the novelty of ideas generated in the AUT but had no significant effect on performance during idea selection.</p><p><strong>Conclusion: </strong>The cognitive control mechanisms of the left DLPFC and IFG differ during the creative process. Anodal stimulation of the left DLPFC enhances goal-directed cognitive control, thereby promoting creativity, whereas cathodal stimulation of the left IFG facilitates the generation of creative ideas by releasing inhibitory control over semantic retrieval.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of electroacupuncture on neural function and the expression of inflammation-related proteins NLRP3/caspase-1 in rats with ischemic stroke.","authors":"Zhifeng Wang, Yujiang Xi, Junfeng Lan, Jiao Yang, Ting Shi, Shuangfeng Xu, Liwei Xing, Pan Pan, Jian Wang","doi":"10.1097/WNR.0000000000002167","DOIUrl":"10.1097/WNR.0000000000002167","url":null,"abstract":"<p><p>This study aimed to investigate the neuroprotective effects of electroacupuncture (EA) at the Baihui and Dazhui acupoints in a rat model of ischemia-reperfusion injury. Ninety-six male Sprague-Dawley rats were randomly assigned to four groups ( n  = 24 per group): Sham, middle cerebral artery occlusion (MCAO), MCAO+EA, and MCAO+MCC950. The MCAO model was induced using filament embolization. Neurological function was assessed using Zea Longa scores on days 1 and 7 posttreatment, while cerebral infarction volume was measured using 2,3,5-triphenyltetrazolium chloride staining. Gene expression levels of NLRP3 and GSDMD were quantified by RT-qPCR, and protein expressions of NLRP3, GSDMD, caspase-1, IL-1β, and IL-18 were evaluated via Western blotting, immunohistochemistry, immunofluorescence staining, and ELISA. On day 1, compared with the MCAO group, the MCAO+EA and MCAO+MCC950 groups exhibited significantly reduced mRNA and protein expressions of NLRP3 and GSDMD ( P  < 0.05), as well as decreased levels of caspase-1, IL-1β, and IL-18 ( P  < 0.05). However, no significant differences were observed in neurological deficit scores or cerebral infarction volume. By day 7, both the MCAO+EA and MCAO+MCC950 groups showed significant improvements in neurological function ( P  < 0.05), reductions in cerebral infarction volume ( P  < 0.05), and further decreases in the expression of NLRP3, GSDMD, caspase-1, IL-1β, and IL-18 ( P  < 0.05). EA at the Baihui and Dazhui acupoints alleviates neurological deficits in ischemic stroke rats by inhibiting the NLRP3/caspase-1 inflammatory pathway and reducing the expression of apoptosis-related proteins such as NLRP3, GSDMD, caspase-1, IL-1β, and IL-18.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"456-466"},"PeriodicalIF":1.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture promotes functional recovery after spinal cord injury in rats by regulating P2X4R/p38 MAPK signaling pathway and suppressing inflammatory responses.","authors":"Xiang Wang, Yimin Gao, Jianzhong Huo","doi":"10.1097/WNR.0000000000002163","DOIUrl":"10.1097/WNR.0000000000002163","url":null,"abstract":"<p><p>This study aimed to investigate whether electroacupuncture can modulate the purinergic P2X4 receptor (P2X4R)/p38 mitogen-activated protein kinase (MAPK) pathway, thereby reducing inflammatory responses and facilitating functional recovery in a rat model of spinal cord injury (SCI). The SCI model was developed in female rats. The electroacupuncture intervention began on the seventh day after modeling, mainly Jiaji, Dazhui, and Mingmen. Sensory function was evaluated via the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), while motor function was measured using the Basso, Beattie, and Bresnahan (BBB) scoring system and footprint analysis. To analyze the protein expression related to the P2X4R/p38 MAPK signaling pathways, methods such as immunohistochemistry, immunofluorescence analysis, quantitative real-time PCR, and western blotting were utilized. To evaluate the levels of inflammatory cytokines, ELISAs were utilized. Additionally, after hematoxylin and eosin staining, histological alterations in spinal cord tissue were investigated. The results showed that MWT, TWL, and BBB scores were decreased, while P2X4R, phosphorylated-p38 MAPK, and phosphorylated nuclear factor κB p65 expression levels were increased, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels were elevated, and histopathological damage was more pronounced after SCI. However, electroacupuncture treatment effectively reversed these pathological changes. We demonstrate that electroacupuncture can alleviate SCI in rats by inhibiting the activation of the P2X4R/p38 MAPK pathway and reducing inflammatory response.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"443-455"},"PeriodicalIF":1.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of autophagy in the amygdala ameliorates anxiety-like behaviors induced by morphine-protracted withdrawal in male mice.","authors":"Shuang Han, Chenchen Zhu, Dengjun Min, Zicheng Li","doi":"10.1097/WNR.0000000000002166","DOIUrl":"10.1097/WNR.0000000000002166","url":null,"abstract":"<p><strong>Objective: </strong>Morphine withdrawal triggers a range of negative affective states, wherein anxiety is typically common, significantly contributing to the morphine relapse. To date, the exact mechanism underlying morphine withdrawal-induced anxiety has remained unclear. Previous studies have proposed that autophagy is involved in the pathogenesis of morphine addiction and anxiety; however, the possible relationship between autophagy and morphine withdrawal-induced anxiety has not been explored before. In this study, we aimed to reveal the potential role of autophagy in anxiety-like behaviors elicited by protracted morphine withdrawal, and which brain region is involved.</p><p><strong>Methods: </strong>We established the model mice of anxiety by chronic intermittent escalating-dose morphine administration for 7 days and then withdrawing for 4 days. Anxious behaviors were detected using the Open field test and the Elevated plus maze test. Western blot was performed to measure the change of autophagy-associated proteins (ATG5, Beclin-1, LC3) in different brain regions.</p><p><strong>Results: </strong>Our results showed that intraperitoneal injection of an autophagy inhibitor 3-Methyladenine attenuated protracted morphine withdrawal-induced anxiety-like behaviors in male mice. Moreover, protracted morphine withdrawal predominantly promoted autophagy in the amygdala, rather than other related brain regions, suggesting the crucial involvement of amygdala in autophagy-mediated anxiety after morphine withdrawal. We further validated that 3-Methyladenine can effectively reduce autophagy-associated protein levels in the relevant brain region.</p><p><strong>Conclusion: </strong>These findings indicated that protracted morphine withdrawal-elicited autophagy in the amygdala contributes to the anxiety-like behaviors and may have implications for the future treatment of this disorder.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"487-496"},"PeriodicalIF":1.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network centrality alterations in patients with moyamoya disease after combined revascularization surgery: a resting-state fMRI study.","authors":"Yuanyuan Wang, Jian Li, Feng Lin, Junwei Gao, Zihe Xu, Jie Liu, Xianjun Zeng","doi":"10.1097/WNR.0000000000002154","DOIUrl":"10.1097/WNR.0000000000002154","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore alterations in brain network characteristics among patients with moyamoya disease (MMD) before and after combined revascularization surgery (CRS).</p><p><strong>Methods: </strong>This investigation enrolled 20 MMD patients alongside 20 age- and sex-matched healthy controls (HCs). All participants underwent MRI scans. Additionally, MMD patients were subjected to comprehensive clinical assessments. Degree centrality (DC) analysis was utilized to assess the connectivity features of the entire brain network. The study also examined correlations between DC values in MMD patients before- (pre-CRS) and after-CRS (post-CRS) and various clinical indicators.</p><p><strong>Results: </strong>Compared with HCs, pre-CRS MMD patients showed abnormal DC values in multiple brain regions, mainly including the cerebellum, frontal lobe, temporal lobe, and cingulate gyrus. One year after CRS treatment, the DC values of the bilateral cerebellum posterior lobe showed a reverse increase. In addition, the DC value of the right cerebellum posterior lobe in pre-CRS MMD patients was positively correlated with the Montreal cognitive assessment scores.</p><p><strong>Conclusions: </strong>CRS treatment can effectively improve the functional network damage of the bilateral cerebellum posterior lobes caused by MMD, and it is expected to provide a new neuroimaging marker for the evaluation of CRS treatment efficacy.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"435-442"},"PeriodicalIF":1.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mendelian randomization combined with single-cell sequencing data analysis of chemokines and chemokine receptors and key genes and molecular mechanisms associated with epilepsy.","authors":"Lin-Ming Zhang, Tao Zeng, Bing-Ran Zhang, Qiu-Juan Zhang, Shu-Ji Gao, Yan-Lin Zhu, Ming-Wei Liu","doi":"10.1097/WNR.0000000000002168","DOIUrl":"10.1097/WNR.0000000000002168","url":null,"abstract":"<p><strong>Objective: </strong>To explore the functions and potential regulatory mechanisms of chemokine and chemokine receptor (CCR)-related genes in epilepsy.</p><p><strong>Methods: </strong>CCRs were identified as candidate genes and their causal relationship with epilepsy was rigorously evaluated via Mendelian randomization analysis. Subsequently, single-cell RNA sequencing (scRNA-seq) data were analyzed to identify and classify cell clusters into distinct types based on cellular annotation. Differential expression analysis was conducted to pinpoint key genes by overlapping the candidate gene set with differentially expressed genes (DEGs). Furthermore, potential therapeutic drugs for epilepsy were predicted, offering novel avenues for disease management and treatment.</p><p><strong>Results: </strong>In total, 6395 DEGs were identified across the six cell clusters. After their intersection, CCRL2, XCL2, CXCR5, CXCL1, and CX3CR1 were pinpointed as key genes. Microglia, T cells, B cells, and macrophages have been emerged as critical cells. Furthermore, CXCL1 was regulated by hsa-miR-570-3p and hsa-miR-532-5p. Notably, CXCR5, CXCL1, and CX3CR1 were associated with 27 drug compounds. This comprehensive study leveraged scRNA-seq and transcriptomic data to elucidate the roles of CCR-related genes in epilepsy. Notably, CCRL2, XCL2, CXCR5, CXCL1,and CX3CR1 were identified as key genes implicated in epilepsy, whereas microglia, T cells, B cells, and macrophages were recognized as critical contributors to the development of epilepsy.</p><p><strong>Conclusions: </strong>Regulating the expression of CCRL2, XCL2, CXCR5, CXCL1, and CX3CR1, along with the activity of these immune cells may offer therapeutic potential for the alleviation of epilepsy.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"467-486"},"PeriodicalIF":1.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AAV-mediated transgene delivery targeting spiral ganglion nonsensory cells.","authors":"Joshua S Lin, Nhi V Nguyen, Seiji B Shibata","doi":"10.1097/WNR.0000000000002172","DOIUrl":"10.1097/WNR.0000000000002172","url":null,"abstract":"<p><p>In-situ neuronal reprogramming in the cochlea through gene therapy offers an avenue to restore hearing loss caused by neuronal damage. One possible source of neuronal conversion is the nonspiral ganglion cells (NSGCs), which include satellite cells, Schwann cells, and otic mesenchyme cells. A major obstacle for this approach is the vector-mediated transgene delivery toward NSGCs. Herein, we sought to assess the transduction profile of adeno-associated virus (AAV) serotypes with peripheral glial cell tropism in the murine inner ear. AAV-1, AAV-DJ, and AAV-PHP.eB with a cytomegalovirus promoter-driven enhanced green flourescent protein (eGFP) reporter were injected into CBA/CaJ neonatal mice via the posterior semicircular canal. One week postinjection, the cochlear tissue was collected for immunohistochemistry in whole-mount and mid-modiolar sections to assess the colocalization of eGFP within the NSGCs in the osseous spiral lamina and Rosenthal's canal. The contralateral ear served as an internal control. Auditory brain responses (ABRs) were recorded 30 days postinjection to assess for hearing loss. AAV-1 and AAV-DJ demonstrated 30-32% transduction efficacy of Pou3f4 immunopositive otic mesenchyme cells, whereas transduction efficacy of Sox2 or Sox10 positive Schwann cells and satellite cells was 0.8-1.82% for all serotypes. At 30 days postinjection, ABR thresholds in the injected mice were comparable to those of the noninjected control. We were able to transduce otic mesenchyme cells among SGNCs in the spiral ganglion region, whereas transduction of Schwann cells and satellite cells continues to pose challenges with AAV-1, AAV-DJ, and AAV-PHP.eB serotypes.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"497-503"},"PeriodicalIF":1.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in seizure presentation in a Dravet syndrome mouse model.","authors":"Sheryl Anne D Vermudez, Rui Lin, Gabrielle E McGinty, Yongho Choe, Amanda Liebhardt, Benjamin Hui, Ella Lubbers, Sameer C Dhamne, Mustafa Q Hameed, Alexander Rotenberg","doi":"10.1097/WNR.0000000000002159","DOIUrl":"10.1097/WNR.0000000000002159","url":null,"abstract":"<p><strong>Objectives: </strong>Dravet syndrome is an epileptic encephalopathy mostly because of haploinsufficiency of the SCN1A voltage-gated sodium channel subunit. Disease presentation (i.e. severe seizures and early life mortality) is faithfully modeled in mice haploinsufficient in Scn1a ( Scn1a+/ - ). However, the characterization of sex differences in mortality and seizure morbidity is limited. Given the reliance of mouse models for studying disease pathophysiology and for the development of novel treatments, we tested whether disease presentation differed in juvenile and adult female and male Scn1a+/ - mice.</p><p><strong>Methods: </strong>Mortality and seizure morbidity were quantified in juvenile and adult female and male Scn1a+/ - animals on an F1 hybrid C57 × 129S6 background.</p><p><strong>Results: </strong>Mortality was significantly higher in female Scn1a+/ - mice compared with males regardless of age, and juvenile female Scn1a+/ - mice had a significantly lower febrile seizure threshold than age-matched Scn1a+/ - males. Conversely, long-term video EEG recordings revealed that adult male Scn1a+/ - mice had significantly more frequent and longer spontaneous seizures than adult females. Adult female Scn1a+/- mice, however, were significantly more hyperactive, which may indicate sleep impairment.</p><p><strong>Conclusion: </strong>The phenotypic presentation of Scn1a+/ - mice is sex-dependent which may have translational implications for understanding basic pathophysiological mechanisms as well as therapeutic drug discovery in Dravet syndrome.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"383-388"},"PeriodicalIF":1.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}