Brain Research Bulletin最新文献

{"title":"The functional connectivity status of DMN and its anti-correlated networks across cognitive loads in clinical high risk for psychosis","authors":"Ling Quan ,&nbsp;Xiaoying Sun ,&nbsp;Chuan He ,&nbsp;Xiao Guo ,&nbsp;Ting Ye ,&nbsp;Hanxi Wu ,&nbsp;Gujing Li ,&nbsp;Maria Luisa Bringas-Vega ,&nbsp;Sisi Jiang ,&nbsp;Dezhong Yao ,&nbsp;Cheng Luo","doi":"10.1016/j.brainresbull.2025.111709","DOIUrl":"10.1016/j.brainresbull.2025.111709","url":null,"abstract":"<div><div>The abnormal functional integration of DMN was widely observed in the psychosis. However, few studies focused on DMN in individuals at Clinical High Risk for Psychosis (CHR), especially under different cognitive loads. The present research predominantly focused on DMN and its antagonism with other networks using the functional MRI. To characterize the specificity of cognitive load-dependent antagonism between DMN and its anti-correlated networks in CHR, this study simulated a graded cognitive load continuum by implementing resting-state fMRI (Minimal cognitive load), passive SSVEP task (low cognitive load), and Emotional Face-Matching Task (high cognitive load). There were 36 CHR individuals and 39 healthy controls (HC) enrolled. Static and dynamic functional connectivity (sFC and dFC) were analyzed. The CHR subjects exhibited significantly reduced antagonism between higher-order cortices and DMN under low cognitive condition. Conversely, they demonstrated enhanced antagonism with greater fluctuation under high cognitive condition, likely a compensatory mechanism to maintain cognitive performance. Concurrently, the primary cortex demonstrated compensatory fluctuations during low cognitive load task. The neural signature reflects inefficient neural resource allocation and cognitive flexibility deficits, suggesting that dynamic brain network indicators based on cognitive load may become sensitive biomarkers for the early identification and intervention of CHR.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111709"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Charles Bonnet syndrome: An updated review","authors":"Sophia E.G. Christoph ,&nbsp;Karl T. Boden ,&nbsp;Berthold Seitz ,&nbsp;Peter Szurman ,&nbsp;André Schulz","doi":"10.1016/j.brainresbull.2025.111683","DOIUrl":"10.1016/j.brainresbull.2025.111683","url":null,"abstract":"<div><div>Charles Bonnet Syndrome (CBS) is a complex and underrecognized condition characterized by visual hallucinations in individuals with visual impairment but preserved cognitive function. This review examines the evolving definitions, epidemiology, risk factors, and pathophysiological models of CBS. Drawing from a broad range of studies, the review identifies key diagnostic inconsistencies and highlights the syndrome’s multifactorial origins, including sensory deprivation and cortical processing imbalances. Epidemiological data suggest CBS affects up to 10 % of visually impaired individuals, though prevalence estimates vary widely due to definitional discrepancies. Risk factors include low visual acuity, female sex, social isolation, and possibly certain medications, though evidence remains inconclusive. Pathophysiological theories such as deafferentation, predictive coding, and the perception-attention deficit model underscore the interplay between bottom-up and top-down mechanisms in hallucination formation. The review also explores differential diagnoses and discusses therapeutic approaches, including vision restoration, pharmacological agents, and psychoeducation. While no standardized treatment exists, early recognition and patient reassurance can significantly improve outcomes. The review calls for clearer diagnostic criteria, further research into neurobiological mechanisms, and longitudinal studies to better understand the prognosis and potential links between CBS and cognitive decline.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111683"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of changes in late positive potential during emotion regulation: Evidence from a three-level meta-analysis","authors":"Xuejing Zou,&nbsp;Han Xiao,&nbsp;Siyu Di,&nbsp;Haiying Qu","doi":"10.1016/j.brainresbull.2025.111700","DOIUrl":"10.1016/j.brainresbull.2025.111700","url":null,"abstract":"<div><h3>Objective</h3><div>A growing body of research has employed event-related potential (ERP) techniques to investigate emotion regulation. However, studies utilizing consistent indicators have yielded divergent and at times contradictory findings. The primary objectives of this study are to systematically evaluate whether significant changes occur in the amplitude of the late positive potential (LPP), a key ERP component, during emotion regulation, and to further assess the temporal dynamics of LPP modulation across different processing stages.</div></div><div><h3>Methods</h3><div>A total of three databases—PubMed, Web of Science, and PsycINFO—were searched for electroencephalography studies related to emotion regulation published between the year 2000 and March 1, 2025, resulting in the inclusion of 48 studies with 150 effect sizes. This meta-analysis utilized CMA3.0 and R4.5 software. When a study reported multiple effect sizes, a three-level meta-analysis was conducted, and publication bias was assessed using funnel plots, the Egger test at the two- and three-levels.</div></div><div><h3>Results</h3><div>The results indicated significant total effect sizes in the central-parietal region across the full, early, and late time windows, while total effect sizes in other brain regions and time windows did not reach statistical significance.</div></div><div><h3>Conclusions</h3><div>The LPP in the central parietal serves as a reliable electrophysiological indicator of emotion regulation (especially cognitive reappraisal), and differences induced by this emotion regulation are more pronounced in early and late time windows.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111700"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long non-coding RNA THAP7-AS1 interacts with EIF3A and enhances ITPR1 to enhance endoplasmic reticulum stress and endothelial cell pyroptosis in ischemic stroke","authors":"Yini Pan ,&nbsp;Hui Chen ,&nbsp;Jianhua Xu,&nbsp;Li Zhao,&nbsp;Meifen Yao","doi":"10.1016/j.brainresbull.2025.111706","DOIUrl":"10.1016/j.brainresbull.2025.111706","url":null,"abstract":"<div><div>THAP7-AS1 is a newly discovered long non-coding RNA (lncRNA) whose biological roles in human physiological and pathological processes remain elusive. This study explores the functional impacts of THAP7-AS1 and its interacting molecular cascades in human umbilical vein endothelial cell damage in the context of ischemic stroke. We observed that THAP7-AS1 interacted with EIF3A in human umbilical vein endothelial cells through a combination of RNA-IP, pull-down assays, and immunofluorescence staining assays. Knockdown of either THAP7-AS1 or EIF3A led to a significant reduction in ITPR1 expression, a key regulator of Ca^2 + signaling and pyroptosis. In ischemic stroke models induced by oxygen-glucose deprivation (OGD), THAP7-AS1 was upregulated alongside EIF3A and ITPR1, promoting endothelial cell pyroptosis and endoplasmic reticulum (ER) stress. Knockdown of THAP7-AS1 or EIF3A alleviated OGD-induced pyroptosis and ER stress, while overexpression of ITPR1 exacerbated these conditions. <em>In vivo</em>, inhibition of ITPR1 with Xestospongin C reduces brain infarction and pyroptosis markers in stroke mice. These results suggest that the THAP7-AS1/EIF3A/ITPR1 axis plays a crucial role in ischemic stroke, contributing to endothelial cell dysfunction through pyroptosis and ER stress. Targeting this pathway may offer therapeutic potential for stroke-related endothelial injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111706"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of cognitive impairment in chronic kidney disease: A radiomics and machine learning approach with quantitative susceptibility mapping","authors":"Yi-Fan Guo ,&nbsp;Yuan-zhe Li ,&nbsp;Yu Qi ,&nbsp;Xu Liu ,&nbsp;Li-jun Song ,&nbsp;Wen-bo Yang ,&nbsp;Min-gan Li ,&nbsp;Xiao-yan Bai ,&nbsp;Mao-sheng Xu ,&nbsp;Meng-yuan Shen ,&nbsp;Si-qing Cai ,&nbsp;Yi Wang ,&nbsp;Zheng-han Yang ,&nbsp;Zhen-chang Wang ,&nbsp;Hao Wang","doi":"10.1016/j.brainresbull.2025.111714","DOIUrl":"10.1016/j.brainresbull.2025.111714","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) alters magnetic susceptibility within the basal ganglia, contributing to cognitive impairment (CI). This study aims to develop a radiomics-based model using quantitative susceptibility mapping (QSM) and machine learning for diagnosing CKD-related CI.</div></div><div><h3>Method</h3><div>A total of 161 CKD patients were prospectively recruited, with 113 in the training set and 48 in the test set. Radiomic features were extracted from basal ganglia nuclei on QSM images. After preprocessing and feature selection, multiple machine learning algorithms were evaluated. The final radiomics model was selected based on decision curve analysis (DCA) in the test cohort. A combined model was built by integrating clinical characteristics with the radiomics model using multivariable logistic regression. Model performance was assessed using receiver operating characteristic (ROC) analysis and DCA.</div></div><div><h3>Results</h3><div>DCA identified the putamen based support vector machine (SVM) radiomics model as the optimal model. It achieved AUCs of 0.929 (95 % CI 0.870–0.972) in the training set and 0.891 (95 % CI 0.786–0.972) in the test set. The combined model showed further improvement, yielding AUCs of 0.964 (95 % CI 0.928–0.989) and 0.933 (95 % CI 0.856–0.987). DCA indicated the highest net benefit for the combined model.</div></div><div><h3>Conclusion</h3><div>QSM based radiomics of the putamen, especially when combined with clinical characteristics, may serve as a promising noninvasive approach for identifying CKD related CI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111714"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha-Bisabolol alleviates LPS-reduced hippocampal neurogenesis and cognitive function by anti-inflammatory action via downregulating MAPK and NF-κB signaling in mice","authors":"Shintae Kim ,&nbsp;Su-Bin Seong ,&nbsp;Kyung-Joo Seong ,&nbsp;Bo-Ram Mun ,&nbsp;Won-Seok Choi ,&nbsp;Ji-Yeon Jung ,&nbsp;Won-Jae Kim","doi":"10.1016/j.brainresbull.2025.111690","DOIUrl":"10.1016/j.brainresbull.2025.111690","url":null,"abstract":"<div><div>Neuroinflammation is a key pathological process contributing to hippocampal neurogenesis impairment and cognitive dysfunction. This study aimed to evaluate the neuroprotective effects of α-Bisabolol (α-Bis), a natural sesquiterpene alcohol, on lipopolysaccharide (LPS)-induced neuroinflammation in mice. LPS administration decreased neural stem cell (NSC) proliferation, neural differentiation, cognitive dysfunction and increased NSC apoptosis. Oral administration of α-Bis ameliorated LPS-reduced hippocampal NSC proliferation, differentiation, cognitive function and LPS-induced NSC apoptosis. Mechanistically, α-Bis attenuated LPS-enhanced microglial activation and suppressed CD68 ⁺ cells with pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) but increased CD206⁺ cells with anti-inflammatory cytokines (IL-10, TGF-β) expression. In addition, α-Bis inhibited the TLR4/MAPK/NF-κB signaling cascade activated by LPS. These findings suggest that α-Bis confers neuroprotection by promoting anti-inflammatory cytokine expression from CD206⁺ microglia via downregulation of TLR4/MAPK/NF-κB signaling in the hippocampus under LPS-induced neuroinflammation, thereby restoring hippocampal neurogenesis and cognitive function impaired by LPS, highlighting its therapeutic potential for inflammation-associated neurodegenerative diseases.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"234 ","pages":"Article 111690"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic GSK-3β targeting stabilizes multifunctional β-catenin to rescue neuronal and behavioral deficits in fragile X messenger ribonucleoprotein 1 knockout mice","authors":"Siming Zhang ,&nbsp;Peng Xiang ,&nbsp;Mingjiao Suo,&nbsp;Ziyu Yi,&nbsp;Zhen Wei,&nbsp;Jinquan Li,&nbsp;Yan Zeng,&nbsp;Yushan Chen","doi":"10.1016/j.brainresbull.2025.111710","DOIUrl":"10.1016/j.brainresbull.2025.111710","url":null,"abstract":"<div><div>Fragile X syndrome (FXS) is the predominant singlegene cause of inherited intellectual disability and is strongly associated with autism spectrum disorder (ASD). FXS results from the disruption of fragile X messenger ribonucleoprotein 1 gene (FMR1) and is characterized by synaptic dysfunction manifesting as impaired cognitive function and social communication. The Wnt/β-catenin pathway plays a pivotal role in regulating synaptic structural remodeling and functional homeostasis, critically contributing to higher-order neural processes such as learning and memory. Studies have identified glycogen synthase kinase 3 beta (GSK3β), a key negative regulator of Wnt signal transduction, is abnormally activated in the pathophysiology of FXS, and demonstrated that GSK3β inhibition partially rescues cognitive and behavioral deficiencies in FXS mice. However, the spatiotemporal dysregulation of β-catenin dynamics and its synaptic consequences remain poorly understood. Here, we investigated the role and molecular mechanism of Wnt/β-catenin pathway during developmental stages in FXS using <em>Fmr1</em> gene knockout (<em>Fmr1</em> KO) mice. We systematically explored β-catenin homeostasis across subcellular compartments. Our results showed increased phosphorylation of β-catenin at Ser^33,37, Thr⁴¹ and Ser⁵⁵² residues, which fosters its degradation. This was accompanied by reduced levels of active β-catenin in the membrane, cytoplasm and nucleus within the hippocampus (Hipp) and prefrontal cortex (PFC) of <em>Fmr1</em> KO mice. Confocal microscopy further demonstrated diminished co-localization of β-catenin with N-cadherin, leading to compromised intercellular adhesion in both <em>Fmr1</em> KO neurons. Moreover, FXS mice showed impaired neuronal morphology and deficiencies in social and cognitive functions, which were associated with the downregulation of pre- and postsynaptic proteins targeted by Wnt pathway. Strikingly, pharmacological activation of Wnt signal transduction restored β-catenin nuclear translocation and synaptic protein expression, rescued neuronal ultrastructural abnormalities and improvd cognitive and social behaviors. Our findings establish hypoactivity of canonical Wnt signaling as a central mechanism underlying synaptic pathology in FXS, linking β-catenin destabilization to altered neuronal morphology, aberrant synaptic protein networks, and behavioral phenotypes. Consequently, bolstering Wnt pathway may represent a promising neuroprotective strategy for precision intervention in FXS.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111710"},"PeriodicalIF":3.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of angiogenesis in cerebral ischemic rats through ceRNA networks and its impact on cerebral ischemic stroke prognosis","authors":"Wenfeng Cao ,&nbsp;Mingyue Wang ,&nbsp;Wen Chai ,&nbsp;Chaoqun Luo ,&nbsp;Yanmei Wang ,&nbsp;Xinhua Zhou ,&nbsp;Jie Li ,&nbsp;Lingjuan Li","doi":"10.1016/j.brainresbull.2025.111703","DOIUrl":"10.1016/j.brainresbull.2025.111703","url":null,"abstract":"<div><h3>Background</h3><div>Cerebral ischemic stroke (CIS) represents a major cerebrovascular disorder characterized by high incidence and disability rates, significantly compromising patient quality of life and survival. Angiogenesis demonstrates potential for improving post-ischemic cerebral blood flow and reducing infarct volume, though its regulatory mechanisms require further elucidation.</div></div><div><h3>Methods</h3><div>We established a permanent focal middle cerebral artery occlusion (pMCAO) rat model and performed whole transcriptome sequencing. Differential expression analysis identified dysregulated long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Regulatory networks (circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA) were constructed using differential expression data and public databases. mRNAs within networks underwent functional enrichment and protein-protein interaction (PPI) analysis to investigate angiogenic mechanisms.</div></div><div><h3>Results</h3><div>Ischemia-hypoxia altered circRNA, lncRNA, and miRNA expression profiles, modulating angiogenesis through specific pathways. The circRNA/lncRNA-miRNA-mRNA networks implicated angiogenesis-related pathways including Cytokine-cytokine receptor interaction and cAMP signaling pathway. Key miRNAs (rno-miR-665, rno-novel-108-mature, rno-novel-82-mature) demonstrated strong angiogenic associations in the ischemia-hypoxia model.</div></div><div><h3>Conclusions</h3><div>This study delineates lncRNA, circRNA, and miRNA regulatory functions in ischemia-hypoxia through network construction, highlighting candidate therapeutic targets. These findings provide novel research directions for promoting angiogenesis and improving CIS prognosis.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111703"},"PeriodicalIF":3.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of SCD1 attenuates neuroinflammation and brain injury after cerebral ischemia-reperfusion","authors":"Shuangkai Li ,&nbsp;Xiang Li Jr ,&nbsp;Lu Peng ,&nbsp;Haojie Ding ,&nbsp;Xuan Shi ,&nbsp;Jiale Liu ,&nbsp;Haiying Li ,&nbsp;Jianguo Xu ,&nbsp;Qing Sun","doi":"10.1016/j.brainresbull.2025.111693","DOIUrl":"10.1016/j.brainresbull.2025.111693","url":null,"abstract":"<div><div>Neuroinflammation mediated by microglial hyperactivation represents a pivotal pathological mechanism exacerbating neuronal damage following cerebral ischemia. Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis, plays a crucial regulatory role in metabolic and inflammatory processes. However, its specific function in post-ischemic neuroinflammation remains incompletely understood. This study found that SCD1 was highly expressed in the penumbra region following middle cerebral artery occlusion/reperfusion (MCAO/R) in mice. Then, we systematically evaluated the role of SCD1 in regulating neuroinflammation after cerebral ischemia–reperfusion and explored its underlying mechanisms through administrating SCD1-specific inhibitor CAY10566. Results showed that CAY10566 significantly reduced level of pro-inflammatory cytokines and infarct volume after cerebral ischemia–reperfusion. Furthermore,suppression of SCD1 also alleviated neuronal apoptosis and improved cognitive and motor functions after ischemic stroke Mechanistically, the modulation of the NF-κB signaling pathway by SCD1 may involve the participation of TNFR1. Collectively, these findings suggested that the SCD1 may serve as a critical checkpoint regulating NF-κB signaling in cerebral ischemia–reperfusion injury. Targeting SCD1 may represent a promising therapeutic strategy for ischemic stroke.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111693"},"PeriodicalIF":3.7,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism by which puerarin inhibits neuroinflammation and alleviates lipopolysaccharide-induced anxiety-like behavior in mice via modulating gut microbiota based on the brain-gut axis theory","authors":"Ge Wang ,&nbsp;Qisheng Tang ,&nbsp;Dan Wang","doi":"10.1016/j.brainresbull.2025.111698","DOIUrl":"10.1016/j.brainresbull.2025.111698","url":null,"abstract":"<div><h3>Background</h3><div>The gut-brain axis (GBA) has been increasingly recognized as a potential contributor to anxiety pathophysiology. Puerarin possesses anti-inflammatory, antioxidant, and neuroprotective properties, but its anxiolytic mechanism via the GBA remains unclear. The intervention of puerarin on lipopolysaccharide (LPS)-induced anxiety-like behavior (ALB) in mice was investigated based on the GBA theory.</div></div><div><h3>Methods</h3><div>Forty mice were allocated at random: control, LPS, LPS+PueL (low-dose puerarin), and LPS+PueH (high-dose puerarin) groups (n = 10 each). ALB was evaluated by the elevated plus maze (EPM). Inflammatory cytokines were measured by ELISA. Tight junction proteins were detected by qPCR and Western blot. Gut microbiota (GM) was analyzed by 16S rRNA sequencing.</div></div><div><h3>Results</h3><div>Compared with the Control, open arm entries (OAE) and open arm time (OAT) were decreased, inflammatory cytokine levels were elevated, intestinal tight junction protein expression was down-regulated, microbial diversity was reduced, and the abundance of pro-inflammatory bacterial genera was obviously increased in the LPS. In the LPS+PueH, OAE and OAT, inflammatory cytokine levels, tight junction protein expression, microbial diversity, and abundance of beneficial bacterial genera were evidently improved (<em>P</em> &lt; 0.05). Correlation analysis revealed that <em>Lactobacillus</em> and <em>Akkermansia</em> were positively correlated with OAE and OAT, whereas <em>Escherichia-Shigella</em> was negatively correlated (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Puerarin alleviated LPS-induced ALB in mice by suppressing neuroinflammation, restoring intestinal barrier integrity, and modulating GM balance, which was closely associated with GBA regulation.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"235 ","pages":"Article 111698"},"PeriodicalIF":3.7,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}