Brain and Behavior最新文献

{"title":"KEAP1-NRF2/HO-1 Pathway Promotes Ferroptosis and Neuronal Injury in Schizophrenia","authors":"Feng Zhu,&nbsp;Tangqun Dan,&nbsp;Shuguang Hua","doi":"10.1002/brb3.70311","DOIUrl":"https://doi.org/10.1002/brb3.70311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study investigates the role of the KEAP1-NRF2/HO-1 signaling pathway in inducing ferroptosis and contributing to neuronal damage in schizophrenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrieved schizophrenia-related data and ferroptosis-related genes from the RNA microarray dataset GSE27383 and FerrDB database, respectively. Bioinformatics data identified KEAP1 as a downregulated gene, which was validated using qRT-PCR and Western blot. We assessed intracellular Fe²⁺ content, MDA levels, GSH, and GPX4 in the prefrontal cortex and peripheral blood mononuclear cells (PBMCs) of patients with schizophrenia. Cortical interneurons (cINs) were generated from human-induced pluripotent stem cells (hiPSCs) of patients with schizophrenia and used to explore KEAP1 alterations during neurodevelopment. In addition, KEAP1 overexpression was induced in cINs via transfection with pcDNA KEAP1. The intracellular Fe⁺ levels, oxidative stress indicators, lipid peroxidation, and inflammatory cytokines were measured after transfection. To investigate molecular mechanisms, KI696—a high-affinity probe that disrupts the KEAP1–NRF2 interaction—was applied, and changes in oxidative stress, lipid peroxidation (C11-BODIPY staining), iron metabolism, and inflammatory pathways were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with schizophrenia exhibited underexpression of KEAP1, a key regulator of ferroptosis, along with elevated intracellular Fe²⁺ levels and increased MDA concentrations, indicating enhanced lipid peroxidation and oxidative stress. Reduced GPX4 activity and GSH levels were also observed, suggesting an increased susceptibility to ferroptosis. To further explore this, cINs derived from hiPSCs of patients with schizophrenia were studied. These cells showed decreased KEAP1 expression. Overexpression of KEAP1 in cINs led to a reduction in intracellular Fe²⁺ concentrations and oxidative damage, highlighting KEAP1's regulatory role in ferroptosis. In addition, treatment with KI696 induced significant alterations in pathways related to oxidative stress, iron metabolism, antioxidant defenses, and inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings indicate that the KEAP1-NRF2/HO-1 pathway contributes to ferroptosis and neuronal injury in schizophrenia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Warning of Neutrophil-to-Lymphocyte Ratio for Neurological Recovery in Acute Ischemic Stroke After Thrombolysis: A Retrospective Study","authors":"Yiran Zhao,&nbsp;Xu Wang,&nbsp;Wenxiu Qin,&nbsp;Shaojing Shi,&nbsp;Min Wang,&nbsp;Jinsheng Zhang,&nbsp;Xin Zou,&nbsp;Junfeng Xu,&nbsp;Jing Li,&nbsp;Xuemin Shi","doi":"10.1002/brb3.70373","DOIUrl":"https://doi.org/10.1002/brb3.70373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To investigate the relationship between dynamic changes in the neutrophil-to-lymphocyte ratio (NLR) and neurological recovery in noninfected patients with acute cerebral infarction after thrombolysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective analysis was conducted on 277 patients with stroke thrombolysis. Least absolute shrinkage and selection operator (LASSO) regression was used to identify factors influencing recovery, and 1:1 propensity matching was performed between the groups to compare the changes in the National Institutes of Health Stroke Scale (NIHSS) score, muscle strength, and NLR after treatment. The receiver operating characteristic (ROC) curve was used to determine the cutoff value of NLR reduction after treatment, which serves as a diagnostic criterion for neurologic recovery. The posttreatment NLR reduction values were categorized according to whether they were equal to and greater than the cutoff value. Logistic regression was performed after intergroup matching to analyze the relationship between NLR and NIHSS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The LASSO regression suggests that increased disease duration and atrial fibrillation are risk factors for neurologic recovery, whereas prolonged treatment duration and increased NLR reduction value are protective factors. Compared with the low-efficacy group, the high-efficacy group exhibited significantly lower NIHSS scores, NLR, and upper and lower extremity muscle strength scores after treatment (<i>p</i> &lt; 0.05). The NLR reduction value was positively correlated with the NIHSS score reduction value and the change in the NIHSS score reduction rate (<i>p</i> &lt; 0.001). The ROC curve and logistic regression indicated that patients with an NLR reduction value of ≥ 0.335 had good recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher NLR reduction values indicate an improved neurologic prognosis after treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial registration</h3>\u0000 \u0000 <p>Clinical Retrospectively Registered Trials: ChiCTR2100045415</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Graph Theory Mechanisms of Fluid Intelligence in the DLPFC: Insights From Resting-State fNIRS Across Various Time Windows","authors":"Yuemeng Wang,&nbsp;Zhencai Chen,&nbsp;Ziqi Cai,&nbsp;Wenqun Ao,&nbsp;Qi Li,&nbsp;Ming Xu,&nbsp;Suyun Zhou","doi":"10.1002/brb3.70386","DOIUrl":"https://doi.org/10.1002/brb3.70386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Brain imaging technologies can measure fluid intelligence (gF) levels more directly, objectively, and dynamically, compared to traditional questionnaire scales. To clarify the temporal mechanisms of graph theory in measuring gF, this study investigated the relationship between graph theoretical indicators in the dorsolateral prefrontal cortex (DLPFC) and gF levels under various time windows.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using 30-min resting-state fNIRS (rs-fNIRS) data and Raven's Advanced Progressive Matrices from 116 healthy participants, the relationship between individual gF levels and DLPFC brain signals was analyzed using average degree (AD) and global efficiency (Eglob).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AD and Eglob in the resting-state DLPFC were significantly negatively correlated with the RAPM score. Considering the effectiveness and efficiency of gF measurement, a 2-min data collection might suffice, while for Eglob, more than 15-min collection was more effective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings help clarify brain indicators and demonstrate the effectiveness of rs-fNIRS in intelligence measurement, providing a theoretical and practical basis for portable and objective gF assessment\u0000.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive Outcomes in Myelin Oligodendrocyte Glycoprotein-IgG Associated Disease Compared to Multiple Sclerosis","authors":"Eileen Galvani,&nbsp;Jeffrey A. Cohen,&nbsp;John T. Martin,&nbsp;Kunio Nakamura,&nbsp;Amy Kunchok,&nbsp;Rachel Galioto","doi":"10.1002/brb3.70310","DOIUrl":"https://doi.org/10.1002/brb3.70310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Little is known about cognitive outcomes in people with myelin oligodendrocyte glycoprotein-IgG associated disease (pwMOGAD). While there are similarities between MOGAD and multiple sclerosis (MS), further evaluation is needed to establish the distinct cognitive trajectories for each disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective review of subjective cognitive changes was performed for adult pwMOGAD. Subsets of pwMOGAD completed a cognitive screening measure and/or comprehensive neuropsychological testing. Their performance was compared to age, sex, and race matched people with MS (pwMS; 3:1 ratio).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Approximately half (51.6%) of pwMOGAD (<i>n</i> = 63) endorsed cognitive dysfunction. On a cognitive screening measure (Processing Speed Test [PST]), performance did not statistically differ between pwMOGAD (<i>n</i> = 36; <i>M</i> = −0.06, SD = 1.36) and pwMS (<i>n</i> = 108; <i>M</i> = −0.04, SD = 1.30), <i>t</i>(62.35) = 0.18, <i>p</i> = 0.86. Of the pwMOGAD who completed neuropsychological testing (total <i>n</i> = 14), 57% demonstrated cognitive impairment on at least one test, and 36% demonstrated impairment on two or more tests. These rates did not differ from pwMS. In pwMOGAD, deficits were most common in processing speed (38.5%) and verbal fluency, spatial judgment, and immediate list recall (14.3% each). PwMOGAD performed better than pwMS on measures of visuomotor processing speed (<i>β</i> = −0.378, <i>t</i> = −2.68, <i>p</i> = 0.01) and cognitive flexibility (<i>β</i> = −0.33, <i>t</i> = −2.27, <i>p</i> = 0.03) after controlling for age, sex, race, education, and disease duration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Subjective cognitive complaints and objective cognitive deficits were common among pwMOGAD. Approximately one-third of pwMOGAD demonstrated clinically significant cognitive impairment (2+ tests impaired) and individual level deficits were most common on measures of processing speed, verbal fluency, spatial judgment, and word list recall.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70310","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Prevalence and Associated Factors of Domestic Violence Against Pregnant Women During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis","authors":"Kosar Miraei Mohammadi,&nbsp;Zohreh Shahhosseini,&nbsp;Mahtab Haji Mohammadreza,&nbsp;Fatemeh Heshmatnia,&nbsp;Roya Nikbakht,&nbsp;Erfan Ghasemi,&nbsp;Maryam Jafari,&nbsp;Hamed Milani,&nbsp;Marzieh Azizi","doi":"10.1002/brb3.70345","DOIUrl":"https://doi.org/10.1002/brb3.70345","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Domestic violence (DV) against women has been reported increasingly, especially during the pandemic worldwide. Exposure to DV during pregnancy is associated with various maternal and neonatal adverse consequences. Therefore, the current study aims to systematically investigate and analyze the prevalence and associated factors of DV or intimate partner violence (IPV) against pregnant women during the COVID-19 pandemic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this systematic review and meta-analysis, systematic literature searches in electronic databases, including Google Scholar, PubMed, Web of Science, Scopus, ScienceDirect, and Scientific Information Database, were conducted from December 2023 to May 2024. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale for cross-sectional and cohort studies. All included studies were entered into a meta-analysis. The binomial distribution formula was used to calculate the variance of point prevalence. In addition, meta-regression was used to assess the prevalence of DV based on the sampling place and quality of the included studies. All statistical analyses were performed with Stata version 11.0, Texas, USA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 16 studies included, 156,775 pregnant women participated, and the sample sizes varied from 215 to 77,310 individuals. According to the combining the results of 12 studies, the overall prevalence of physical, psychological, and sexual violence against pregnant women during COVID-19 was estimated at 13.83 (95% CI, 5.92%–21.73%), 40.02% (95% CI, 22.74%–57.30%), and 15.09% (95% CI, 6.49%–23.69%), respectively. The pooled prevalence of the total IPV against pregnant women during COVID-19, according to the combined results of 15 studies, was estimated at 36.82% (95% CI, 22.24%–51.40%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although the prevalence of all types of violence against pregnant women increased during the COVID-19 pandemic compared to other times, the results of the present study indicated that psychological violence was the most common violence reported by pregnant women. Therefore, it seems that identifying high-risk pregnant women as victims of violence is imperative to develop preventive interventions for this vulnerable group globally.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loving-Kindness Meditation: Systematic Review of Neuroimaging Correlates in Long-Term Practitioners and Clinical Implications","authors":"Kiren Bashir,&nbsp;Stephen B. Edstrom,&nbsp;Sara J. Barlow,&nbsp;Danielle Gainer,&nbsp;Jeffrey D. Lewis","doi":"10.1002/brb3.70372","DOIUrl":"https://doi.org/10.1002/brb3.70372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Loving-kindness meditation (LKM), a meditation type focused on nurturing love and compassion for oneself and others, has been shown to provide mental health benefits, and LKM interventions are being investigated for mental disorders. The benefits of long-term practice, such as increased self-compassion, greater cognitive and affective empathy, and prosocial behavior, are proposed to be due to neuroplastic changes that support well-being. This systematic review aims to summarize the differences in brain structure and function in long-term practitioners (LTPs) of LKM versus controls to identify possible underlying mechanisms that support mental health and drive treatment effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The literature search included Google Scholar, PubMed, and APA PsycINFO from inception through November 13, 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After review, five studies (64 LTPs and 67 controls total) were included. Brain regions with between-group differences reported in at least two studies include the superior parietal lobe, inferior frontal gyrus, medial frontal lobe, and insular cortex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These areas are responsible for self-compassion, cognitive and affective empathy, and prosociality—personal qualities believed to be fostered through LKM practice. Longitudinal neuroimaging and neurophysiological studies incorporating LKM interventions for specific mental disorders are needed to further inform the biological basis of these treatments and may provide surrogate outcome measures for future clinical trials to refine this promising treatment modality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Functional Connectivity Patterns of Brain Networks Involved in Motor Planning Underlie Verbal and Spatial Working Memory","authors":"Emilie Marti,&nbsp;Sélim Yahia Coll,&nbsp;Naz Doganci,&nbsp;Radek Ptak","doi":"10.1002/brb3.70376","DOIUrl":"https://doi.org/10.1002/brb3.70376","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Frontoparietal networks (FPN) are well-recognized for their role in high-level cognition, including mental imagery, executive control, and working memory (WM). A prevailing hypothesis advances that these functions evolved from fundamental motor abilities, such as action planning and motor control. However, whether sensorimotor regions of these FPN contribute to the executive components of WM, and whether this contribution is dependent on task modality, remains underexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This study applied analyses of resting-state functional connectivity (rs-FC) to investigate the contribution of FPN regions to WM that have an established role in motor planning. In a sample of 60 healthy individuals, we explored whether performance in verbal and spatial N-back WM tasks is associated with rs-FC of frontoparietal brain regions that exhibit increased activation during motor planning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Finding</h3>\u0000 \u0000 <p>Comparing verbal and spatial N-back tasks revealed that verbal WM was associated with stronger connectivity between the left medial superior frontal gyrus and left inferior parietal lobule (IPL), as well as the right IPL and the left superior parietal lobule. In contrast, spatial WM was linked to stronger connectivity between the right middle frontal and inferior temporal gyrus, as well as the left occipital pole and postcentral gyrus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings reveal distinct FC patterns underlying verbal and spatial WM and highlight the contribution of brain regions that are important for motor planning to modality-specific WM processes, such as information updating.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelioration of Central Nervous System Autoimmunity Through FFAR2 Agonism Is Associated With Changes in Gut Microbiota","authors":"Bojan Jevtić,&nbsp;Goran Stegnjaić,&nbsp;Suzana Stanisavljević,&nbsp;Milica Lazarević,&nbsp;Filip Nikolić,&nbsp;Graeme L. Fraser,&nbsp;Đorđe Miljković,&nbsp;Mirjana Dimitrijević","doi":"10.1002/brb3.70350","DOIUrl":"https://doi.org/10.1002/brb3.70350","url":null,"abstract":"<p><b>Purpose</b>: The intestinal immune compartment is increasingly recognized as an important player in central nervous system (CNS) autoimmunity. We have recently reported that oral administration of the free fatty acid receptor 2 (FFAR2) agonist Cpd1 in the inductive phase of experimental autoimmune encephalomyelitis (EAE) in rats ameliorates the disease by stimulating the regulatory immune response in the intestine.</p><p><b>Method</b>: Here, the effects of Cpd1 on the gut microbiota and short-chain fatty acid (SCFA) composition were investigated in the same experimental system.</p><p><b>Finding</b>: Increased levels of the phylum <i>Proteobacteria</i>, the class <i>Gammaproteobacteria</i>, the orders <i>Burkholderiales</i> and <i>Erysipelotrichales</i>, the families <i>Sutterellaceae</i> and <i>Erysipelotrichaceae</i>, and the genera <i>Parasutterella</i> and <i>Faecalibaculum</i> were observed in agonist-treated rats. The genera <i>Allobaculum</i> and <i>Ileibacterium</i> were only detected in the agonist-treated group. The treatment led to changes in the functional profile of the gut microbiota both in the KEGG orthologous pathways and in the clusters of orthologous genes. In addition, an altered profile of intestinal SCFA content was observed in the agonist-treated group.</p><p><b>Conclusion</b>: The effects of Cpd1 on the gut microbiota and SCFA composition are relevant to the observed treatment benefit of FFAR2 agonism in the EAE model during the inductive phase of the disease.</p>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Brain-derived Neurotrophic Factor Polymorphisms With Alcohol Use Disorder: An Updated Meta-Analysis of Genetic Association Studies","authors":"Anorut Jenwitheesuk,&nbsp;Noel Pabalan,&nbsp;Pairath Tapanadechopone,&nbsp;Hamdi Jarjanazi,&nbsp;Kittipun Arunphalungsanti,&nbsp;Phuntila Tharabenjasin","doi":"10.1002/brb3.70359","DOIUrl":"https://doi.org/10.1002/brb3.70359","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Brain-derived neurotrophic factor (BDNF) has been proposed to play a role in chronic alcohol consumption. However, studies investigating the association of single nucleotide polymorphisms (SNPs) in the &lt;i&gt;BDNF&lt;/i&gt; gene with alcohol use disorder (AUD), including alcohol dependence, have obtained inconsistent results. This meta-analysis aims to examine the role of &lt;i&gt;BDNF&lt;/i&gt; SNPs (rs6265, rs16917204, rs7103411, and rs11030104) in the risk of AUD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Materials and Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A multidatabase search identified 17 articles (20 studies) for inclusion. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations using standard genetic models (homozygous, recessive, dominant, and codominant). Significant associations were defined as those with a &lt;i&gt;p&lt;/i&gt;-value ≤ 0.05 after applying the Bonferroni correction (&lt;i&gt;p&lt;/i&gt;&lt;sup&gt;BC&lt;/sup&gt;). Subgroup analysis was conducted based on ethnicity (Caucasian and Asian populations). Sources of heterogeneity were investigated through outlier treatment and meta-regression analysis. Only significant outcomes were further subjected to sensitivity analysis and assessment of publication bias.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This meta-analysis generated four significant pooled ORs, representing the core outcomes, all of which indicated reduced risks. Overall, the results indicated a significant association between the &lt;i&gt;BDNF&lt;/i&gt; polymorphism and the risk of AUD in homozygous (OR = 0.72, 95% CIs = 0.60–0.85, &lt;i&gt;p&lt;/i&gt;&lt;sup&gt;BC&lt;/sup&gt; = 0.0038) and codominant (OR = 0.84, 95% CIs = 0.78–0.91, &lt;i&gt;p&lt;/i&gt;&lt;sup&gt;BC&lt;/sup&gt; = 0.0019) model. In subgroup analysis by ethnicity, homozygous (OR = 0.59, 95% CIs = 0.44–0.78, &lt;i&gt;p&lt;/i&gt;&lt;sup&gt;BC&lt;/sup&gt; = 0.0057) and recessive (OR = 0.61, 95% CIs = 0.46–0.81, &lt;i&gt;p&lt;/i&gt;&lt;sup&gt;BC&lt;/sup&gt; = 0.0133) models of &lt;i&gt;BDNF&lt;/i&gt; polymorphisms were significantly associated with a reduced risk of AUD in Caucasians. However, no significant associations were found in Asians. Meta-regression analysis did not identify any covariates that significantly contributed to the observed heterogeneity. The core significant associations were robust and showed no evidence of publication bias.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The current meta-analysis suggests that the examined &lt;i&gt;BDNF&lt;/i&gt; SNPs have a protective effect in the overall analysis (homozygous and codominant) and in the Caucasians subgroup (homozygous and recessive) while the Asians exhibited no effects of &lt;i&gt;BDNF&lt;/i&gt; SNPs on AUD. &lt;i&gt;BDNF&lt;/i&gt; ","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70359","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Preliminary Study of Effect of Melatonin on Inflammation and Hypoxia-Related Factors in a Mouse Model of Elastase-Induced Intracranial Aneurysm","authors":"NarenYa,&nbsp;Yan Feng,&nbsp;Yongxing Su,&nbsp;Le Chen,&nbsp;Yan Liu,&nbsp;Zhongwu Sun,&nbsp;Zhengfei Ma","doi":"10.1002/brb3.70371","DOIUrl":"https://doi.org/10.1002/brb3.70371","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Intracranial aneurysms (IAs) are relatively common cerebrovascular anomalies. Melatonin could modulate inflammatory and offers neuroprotective effects, and its role in IA has not been fully elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An elastase-induced IA mouse model was constructed and melatonin (150 mg/kg) was administered to investigate its therapeutic effects on IA. Aneurysm formation was observed by bromophenol blue gelatin perfusion, and the pathology changes in IA mice were examined using hematoxylin-eosin (HE) staining. The potential mechanisms of melatonin treatment of IA were explored using western blot, enzyme-linked immunosorbent, real-time qPCR, immunohistochemistry, and flow cytometry. An H₂O₂-reduced human brain vascular smooth muscle cells (HBVSMC) injury model was also constructed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The formation of aneurysms was observed in the circle of Willis in the IA mice. Melatonin treatment alleviated the thinning of blood vessel walls and disruption of the internal elastic lamina in IA mice. The levels of Bcl-2 were significantly increased and Bax and cleaved caspase-3 were decreased in IA mice with melatonin treatment, suggesting reduced apoptosis. Furthermore, melatonin reduced levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in IA mice. The H₂O₂-reduced HBVSMCs model showed consistent results. Melatonin reduced levels of krüppel-like factor 6 (KLF6) in IA mice. Importantly, melatonin significantly reduced levels of regulatory T cells (Treg), hypoxia-inducible factor (HIF)-1α, nuclear factor interleukin 3-regulated (NFIL3), TCDD-inducible poly-ADP-ribose polymerase (TIPARP), and increased levels of monocytes in IA mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Melatonin mitigates IA injury by modulating immune cells and hypoxia-related factors. These findings provide an exploratory foundation for therapeutic strategies in IA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}