Brain and Behavior最新文献

{"title":"Tangeretin Improves the Memory of Swiss Mice, Suggesting Potential Molecular Interventions Through Animal Behavior Assessments and In Silico Studies","authors":"Md. Sakib Al Hasan,&nbsp;Mohd Shahnawaz Khan,&nbsp;Arusha Ayub,&nbsp;Raihan Chowdhury,&nbsp;Emon Mia,&nbsp;Md. Shadin,&nbsp;Md. Showkot Akbor,&nbsp;Muhammad Torequl Islam,&nbsp;Md. Shimul Bhuia","doi":"10.1002/brb3.70516","DOIUrl":"https://doi.org/10.1002/brb3.70516","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Tangeretin (TAN), a polymethoxylated flavone from citrus peels, exhibits neuroprotective, anti-inflammatory, and antioxidant properties. This study aims to evaluate the memory-enhancing effects of TAN in <i>Swiss</i> mice and explore its potential molecular interactions with the D₂ dopamine (DOP) receptor through in vivo behavioral assessments and in silico approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p><i>Swiss</i> mice were administered TAN (10 and 20 mg/kg), DOP (22 mg/kg), and olanzapine (OLN) (2 mg/kg), alone and in combinations per orally (p.o.), followed by cognitive assessments using marble burying, dust removal, and trained swimming tests. In silico studies included molecular docking against the D₂ receptor (PDB: 6CM4), pharmacokinetics (SwissADME, pkCSM), and toxicity predictions (ProTox-3).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TAN significantly (<i>p</i> &lt; 0.05) improved cognitive functions, including memory, anxiety, and motor coordination, in a dose-dependent manner, with 20 mg/kg showing the most notable effect. The combination of TAN-10 with DOP-22 enhanced these benefits, whereas TAN-10 with OLN-2 reduced cognitive improvements. TAN-treated Swiss mice showed better performance in marble burying, dust removal, and trained swimming tests, indicating enhanced memory, problem-solving, and motor coordination. These results suggest TAN's potential in cognitive enhancement, particularly with DOP-22. No deaths were observed in any treatment group, and all treated animals exhibited normal physiological activity with no signs of acute toxicity. In silico studies revealed that TAN exhibited the strongest binding affinity (BA) (−6.6 kcal/mol) with the D₂ receptor, forming multiple hydrogen bonds (HBs), which indicates its potential mechanism for memory enhancement via dopaminergic modulation. Pharmacokinetic analyses also showed that TAN has favorable ADMET properties, including high gastrointestinal absorption, blood–brain barrier penetration, and low toxicity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight TAN's potential as a promising therapeutic candidate for memory-related disorders, warranting further clinical exploration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70516","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904904","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":"Insomnia Associated With Increased Risk of Atopic Dermatitis: A Two-Sample Mendelian Randomization Study","authors":"Xiuqin Ni,&nbsp;Xing Li,&nbsp;Jiaxin Li","doi":"10.1002/brb3.70512","DOIUrl":"https://doi.org/10.1002/brb3.70512","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The causal relationships between sleep traits and allergic diseases remain unclear. This study sought to explore their causal associations using Mendelian randomization (MR) analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study utilized summary-level data from genome-wide association studies (GWAS) and selected genetic variants associated with sleep traits as instrumental variables (IVs). For the primary analysis, the inverse-variance weighted (IVW) method was utilized. To further evaluate causal effects, we applied weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses, such as linkage disequilibrium score (LDSC) regression, MR-Egger regression, Cochran's Q test, leave-one-out analysis, and MR-PRESSO, were carried out to confirm result robustness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IVW analysis revealed that genetically predicted insomnia was causally associated with a higher risk of atopic dermatitis (OR = 1.79, 95% CI: 1.17-2.74, P = 0.01), and preferring an evening chronotype was causally associated with a lower risk of allergic rhinitis (IVW: OR = 0.99, 95% CI: 0.99-1.00, P = 0.02). The LDSC analysis further identified a significant genetic correlation between insomnia and atopic dermatitis (r_g = 0.107, P = 0.039), but not between chronotype and allergic rhinitis (r_g = -0.036, P = 0.339). No significant connections were identified between other sleep traits and allergic diseases. The MR-Egger intercept test did not indicate pleiotropy, except for the association with allergic asthma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Chronotype and insomnia were causally associated with the efficacy of sleep-based interventions in allergic disease management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70512","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905025","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 Targets of Deep Brain Stimulation in the Treatment of Treatment-Resistant Depression: A Review","authors":"Jianyang Dong,&nbsp;Mengying Dai,&nbsp;Zinan Guo,&nbsp;Ting Xu,&nbsp;Fangming Li,&nbsp;Jianjun Li","doi":"10.1002/brb3.70505","DOIUrl":"https://doi.org/10.1002/brb3.70505","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The purpose of this review is to evaluate the current state and potential future directions of deep brain stimulation (DBS) therapy for treatment-resistant depression (TRD), a condition that significantly impacts patients' quality of life and for which conventional treatments are often ineffective.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This review synthesizes evidence from clinical trials and preclinical studies published in five years, identified through PubMed searches using keywords (“Deep Brain Stimulation” OR DBS) AND (“Treatment-Resistant Depression” OR TRD). Included studies encompassed clinical research (randomized/non-randomized trials, cohort studies) and mechanistic preclinical studies, excluding non-English publications and nonhuman experiments. Screening prioritized neuroanatomical targets (e.g., SCG, NAcc) and stimulation parameter optimization data. Examining the therapeutic mechanisms of DBS, the neuroanatomical targets utilized, and the clinical outcomes observed. It also discusses the challenges faced in DBS application and proposes potential technological advancements, such as closed-loop therapy and fiber tracking technology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Finding</h3>\u0000 \u0000 <p>Preliminary evidence exists regarding the efficacy and safety of DBS in the treatment of TRD in the subcortical cingulate gyrus (SCG), nucleus accumbens (NAcc), ventral capsule/ventral striatum (VC/VS), anterior limb of the internal capsule (ALIC), and so forth. Nevertheless, the optimal stimulation target remains undetermined. The review highlights the complexity of TRD and the need for personalized treatment strategies, noting that genetic, epigenetic, and neurophysiological changes are implicated in DBS's therapeutic effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, while DBS for TRD remains an experimental therapy, it offers a unique and potentially effective treatment option for patients unresponsive to traditional treatments. The review emphasizes the need for further research to refine DBS targets and parameters, improve patient selection, and develop personalized treatment plans to enhance efficacy and safety in TRD management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70505","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905023","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":"Causality Between Irritable Bowel Syndrome and Suicide Attempt: A Mendelian Randomization Study","authors":"Zhen Deng,&nbsp;Kai Wang,&nbsp;Tianshu Hou","doi":"10.1002/brb3.70513","DOIUrl":"https://doi.org/10.1002/brb3.70513","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prior research has indicated a correlation between irritable bowel syndrome (IBS) and suicidal behavior. Nevertheless, it remains uncertain if this correlation implies causation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used univariate and multivariate Mendelian randomization. The United Kingdom Biobank provided 53,400 European patients and 433,201 European controls for the IBS GWAS. The outcome variable was developed from a genome-wide association analysis of 26,590 suicide attempt cases and 492,022 controls from the International Suicide Genetics Consortium. BioBank Finland GWAS data (9,771 cases and 402,410 controls) was used for SA validation. Primarily employing inverse variance weighting (IVW), we conducted the analysis to establish causality. MR-Egger and weighted median were used as complementary methods to reinforce the robustness and validity of the results. We used the MRlap method to eliminate the effect of sample overlap. We also used a multivariable MR approach to control for the influence of potential confounders. Using a number of approaches, including the Cochran's Q test, the MR-Egger intercept, and the MR-PRESSO methodology, the study examined pleiotropy and heterogeneity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We discovered evidence for an elevated risk of suicide attempt with IBS (OR = 1.67, 95% CI = 1.21–2.35, P = 5.52E–07). MRlap analyses similarly support this result. We got the same results with the validation data (OR = 1.19, 95% CI = 1.06–1.34, P = 2.46E–03). The relationships between the different sensitivity analysis approaches were similar, and there was no indication that outliers influenced these correlations. The independent causal impact of IBS on suicide attempts was maintained after controlling for anxiety, depression, and abdominal pain. In reverse MR, we found no causal link between suicide attempt and IBS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our MR analysis indicates a causal relationship between IBS and suicide risk. Early detection and intervention in suicidal ideation in IBS patients reduces their suicide risk. More study is needed to understand the mechanisms that link IBS and suicidal behavior, which may alter or broaden therapy for specific individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905049","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 Causal Relationship Between Neurotrophic Factors and Delirium: A Mendelian Randomization Study","authors":"Han Wu,&nbsp;Ruilai Jiang,&nbsp;Xiaocheng Huang,&nbsp;Xiaogang Hu","doi":"10.1002/brb3.70494","DOIUrl":"https://doi.org/10.1002/brb3.70494","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Several observational studies have revealed that different neurotrophic factors (NTFs) are associated with delirium, yet the direction and magnitude of the causal association remain poorly understood. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between these factors and delirium.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GWAS data for delirium were sourced from the FINN10 database; GWAS data for risk factors (protein kinase C-binding protein NELL1, neurotrophin-3, neurotrophin-4, brain-derived neurotrophic factor levels, nerve growth factor, ciliary neurotrophic factor, and glial cell-derived neurotrophic factor levels) were from the IEU Open GWAS. Inverse-variance weighted (IVW) was used as a primary analysis. MR-Egger, weighted median (WM), and weighted model were applied to validate the robustness of the results. The MR-Egger regression method was used to explore the presence of horizontal pleiotropy, and the MR pleiotropy residual sum, and outlier (MR-PRESSO) method was applied to detect potential outliers. Cochran's Q test assessed heterogeneity among instrumental variables (IVs). The leave-one-out (LOO) method was used to enhance the precision and veracity of our findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IVW analyses revealed no association between risk factors and delirium. MR Egger, WM, and the weighted mode approach further confirmed these data. MR-Egger regression analysis confirmed the absence of directional pleiotropy in our analysis. Heterogeneity and sensitivity analyses showed reliable results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>No association between other factors and delirium was identified; however, further research is needed to determine if these results apply to other races. Also, advances in molecular biology and epigenetics may shed light on this topic.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905110","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":"Validation of the Spanish Version of the Headache Impact Test (HIT-6) in Patients With Episodic Migraine","authors":"Yaiza Colorado-Martín,&nbsp;Daniel Pecos-Martín,&nbsp;Nerea de Miguel-Hernando,&nbsp;Rubén Cámara-Calmaestra,&nbsp;Daniel Rodríguez-Almagro,&nbsp;Alejandro Ferragut-Garcías,&nbsp;Eduardo Castro-Martín,&nbsp;Alexander Achalandabaso-Ochoa","doi":"10.1002/brb3.70515","DOIUrl":"https://doi.org/10.1002/brb3.70515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The Headache Impact Test (HIT-6) questionnaire is commonly utilized to assess the impact of headaches in both clinical settings and research. To date, no validated Spanish version of this tool has been published.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study seeks to evaluate the psychometric properties of the Spanish version of the HIT-6 questionnaire for use in patients experiencing episodic migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cross-sectional study aimed at validating this measurement instrument. A total of 100 subjects, both male and female, aged 18 to 65 years, diagnosed with episodic migraine, were included in the analysis. Construct validity was assessed using principal component analysis, test-retest reliability via the intraclass correlation coefficient (ICC), internal consistency, and convergent validity against the 12-Item Short Form Health Survey and the Migraine Disability Assessment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The principal component analysis revealed a two-component structure. The overall HIT-6 scale demonstrated strong test-retest reliability ([ICC = 0.89; 95% CI = 0.83–0.92]), with high reliability for the indirect subscale [(ICC = 0.87; 95% CI = 0.81–0.91)] and excellent reliability for the direct subscale [(ICC = 0.90; 95% CI = 0.85–0.93)]. Internal consistency was also robust (Cronbach's <i>α</i> = 0.834), and the questionnaire showed a significant correlation with MIDAS (r = 0.512; <i>p</i> &lt; 0.001), as well as a moderate correlation with the physical (r = -0.326; <i>p</i> &lt; 0.05) and mental factors (r = -0.429; <i>p</i> &lt; 0.001) of the SF-12.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The Spanish adaptation of the HIT-6 questionnaire is a reliable and valid tool for evaluating the impact of episodic migraine on patients' quality of life, confirming the validity of both subscales.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904978","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 Factors and Prognostic Implications of Tumor-Related Epilepsy in Diffuse Glioma Patients: A Real-World Multicenter Study","authors":"Yao Xiao,&nbsp;Zhuang Nie,&nbsp;Jinsha Huang,&nbsp;Jie Zhao,&nbsp;Chengjun Dong,&nbsp;Yan Zou,&nbsp;Zikai Li,&nbsp;Bingqing Yan,&nbsp;Yue Hu,&nbsp;Fan Yang,&nbsp;Jong Woo Lee,&nbsp;Alexander P. Lin,&nbsp;Steven Tobochnik,&nbsp;Min Zhou,&nbsp;Ziqiao Lei","doi":"10.1002/brb3.70510","DOIUrl":"https://doi.org/10.1002/brb3.70510","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose:</h3>\u0000 \u0000 <p>The relevance of tumor-related epilepsy (TRE) to glioma survival is controversial. This study aimed to assess the risk factors and prognostic impact of TRE in adult patients with diffuse gliomas by integrating clinical, radiological, and molecular data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods:</h3>\u0000 \u0000 <p>This multicenter retrospective study included 1036 adult patients with diffuse gliomas from local hospitals and the POLA Network. Patients were categorized into three prognostic groups: lower-grade oligodendroglioma/astrocytoma (OD/AC, II–III, IDH-MT), not otherwise specified or not elsewhere classified (NOS/NEC, II–III, IDH-WT), and high-grade gliomas (HGG, IV). Clinico-radiological, molecular, and therapeutic factors were analyzed using univariate and multivariate logistic regression, with the Cox proportional hazards model applied to identify independent prognostic factors for progression-free survival (PFS) and overall survival (OS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results:</h3>\u0000 \u0000 <p>TRE occurred in 44.4% of OD/AC patients, 25.8% of NOS/NEC patients, and 16.5% of HGG patients. Multivariate analysis identified age as the only significant independent correlate of TRE in the OD/AC group (OR = 0.961; <i>p</i> = 0.004), while the absence of deep structure involvement was independently associated with TRE in the NOS/NEC and HGG groups. In univariate analysis, the presence of TRE was associated with longer PFS and OS across all groups, particularly in the NOS/NEC group, where patients with TRE had a median PFS of 35.2 months compared to 13.6 months in those without TRE (<i>p</i> = 0.02), but was not a significant predictor in multivariate analyses. TRE was the only factor significantly associated with maintaining histological grade at recurrence (HR = 0.094; <i>p</i> = 0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion:</h3>\u0000 \u0000 <p>TRE was not a strong independent prognostic factor after controlling for clinical and molecular tumor features, suggesting that the prognostic relevance of TRE is likely driven by underlying glioma biology and other associated clinical factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905109","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":"Nicotinamide Adenine Dinucleotide Supplementation Improves Cuprizone-Induced Multiple Sclerosis-Related Behavioral Changes in C57BL/6J Mice","authors":"Shuang Song,&nbsp;Ruoyi Guo,&nbsp;Jiangyuan Guo,&nbsp;Bin Li,&nbsp;Yusen Han,&nbsp;Huining Zhang,&nbsp;Li Guo","doi":"10.1002/brb3.70525","DOIUrl":"https://doi.org/10.1002/brb3.70525","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate whether nicotinamide adenine dinucleotide (NAD+) supplementation can improve behavioral changes in a cuprizone-intoxicated mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Six-week-old C57BL/6J mice were divided into three groups: two were fed 0.2% cuprizone chow (cuprizone and cuprizone + NAD+ groups), and the other group was fed normal rodent chow (control group) for 4 weeks. The mice in the cuprizone + NAD+ group received 250 mg/kg/day NAD+ intraperitoneally once a day, while the other mice were administered saline simultaneously. Behavioral tests for spatial memory (Morris water maze and Y maze), locomotor ability (grip test and rotarod test), depression-like behavior (open field test and tail suspension test), and exploratory behavior (open field test) were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the probe test of the Morris water maze, the cuprizone group spent a significantly smaller proportion of time in the target quadrant than the control group did (16.32% vs. 31.66%, <i>p</i> = 0.006). However, supplementation with NAD+ increased the value (28.78% vs. 16.32%, <i>p</i> = 0.023). Similarly, in the Y maze test, the cuprizone group demonstrated a notably lower ratio of effective alterations compared to the control group (0.543 vs. 0.648, <i>p</i> &lt; 0.001), and the cuprizone + NAD+ group presented an improved ratio compared with the cuprizone group (0.613 vs. 0.543, <i>p</i> = 0.021). Compared with the control group, cuprizone toxicity resulted in a decreased time to fall (169.10 vs. 247.60 s, <i>p</i> = 0.015) in the grip test, but NAD+ supplementation mitigated this effect (261.60 vs. 169.10 s, <i>p</i> = 0.003). There were no significant differences in the immobile time among groups in both the tail suspension test and the open field test, and there were also no significant differences in center distance in the open field test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Direct NAD+ supplementation improves the locomotor ability and spatial memory of cuprizone-intoxicated C57BL/6J mice. However, NAD+ supplementation does not show significant effects on depressive and exploratory behavior of experimental mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905027","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":"Analysis and Identification of Therapeutic Targets for Neuronal Regeneration After Ischemic Stroke","authors":"Xiao-Li Min,&nbsp;Li Guo,&nbsp;Zhenyu Wang,&nbsp;Lei Zhao,&nbsp;Chenglong Shi,&nbsp;Xiaoyong Liu,&nbsp;Zhen Wang,&nbsp;Fei-Fei Shang,&nbsp;Jiaping Wang","doi":"10.1002/brb3.70377","DOIUrl":"https://doi.org/10.1002/brb3.70377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study is to analyze and identify genes associated with neuronal regeneration after ischemic stroke (IS) and to predict potential therapeutic targets for neuronal regeneration after IS using bioinformatics analysis methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The GSE137482 and GSE208121 datasets were obtained from the Gene Expression Omnibus (GEO) database, and the differentially expressed hub genes that showed decreased expression in GEO and increased expression in neuronal regeneration after IS were identified as key genes. To identify the key genes, functional enrichment and Protein–Protein Interaction (PPI) network analysis were conducted. The expression levels of the key genes were characterized by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in neuron-induced cell models. Additionally, possible regulatory networks of the key genes were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The screening process yielded 24 differentially expressed pivotal genes, which were predominantly enriched in processes related to epithelial cell proliferation regulation and hormone response. The PPI analysis yielded five key genes (Npas4, Nr4a3, Nr4a1, Egr4, and Egr1), which may exert regulatory roles primarily through peptide and peptide hormone responses. RT-qPCR and western blot assays confirmed that the expression levels of the key genes were elevated in the neuron-like differentiated cell model. However, these findings were inhibited by additional treatment with hypoxia. The analysis of the key gene regulatory network revealed that EGR1 and NR4A1 might regulate hub genes by utilizing their transcription factor properties, with EGR1 being the predominant regulator. The validation results from our cellular model indicated that upregulating EGR1 promotes neuronal-like differentiation in SH-SY5Y cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>EGR1 could potentially serve as a therapeutic target for neuronal regeneration following IS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905273","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":"Rare Variants Cause Charcot-Marie-Tooth Disease in Malian Families","authors":"Abdoulaye Yalcouyé,&nbsp;Lassana Cissé,&nbsp;Salimata Diarra,&nbsp;Seybou H. Diallo,&nbsp;Salia Bamba,&nbsp;Patra Yeetong,&nbsp;Boubacar Maiga,&nbsp;Kékouta Dembélé,&nbsp;Dramane Coulibaly,&nbsp;Salimata Diallo,&nbsp;Abdoulaye Taméga,&nbsp;Alassane Baneye Maiga,&nbsp;Hamidou O. Ba,&nbsp;Vorasuk Shotelersuk,&nbsp;Kenneth H. Fischbeck,&nbsp;Cheick O. Guinto,&nbsp;Guida Landouré","doi":"10.1002/brb3.70496","DOIUrl":"https://doi.org/10.1002/brb3.70496","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction/Aims</h3>\u0000 \u0000 <p>Charcot-Marie-Tooth disease (CMT), the most common inherited peripheral neuropathy, is clinically and genetically heterogeneous with over 100 genes identified to date. Recently, next-generation sequencing (NGS) has enabled molecular diagnosis in previously unidentified CMT cases. However, less progress has been achieved in sub-Saharan African (SSA) populations. We report rare CMT variants found in four unrelated Malian families.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients went through a thorough neurological examination and Nerve Conduction Studies (NCS) were performed. DNA was extracted for genetic analysis (CMT gene panel testing and whole-exome/genome sequencing). Putative variants were confirmed with Sanger sequencing and segregation was checked in all available family members. Deleteriousness was checked using several in silico prediction tools and protein modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nine patients (three males and six females) from four families were enrolled. The mean age at onset and diagnosis were 15 and 22.7 years, respectively (ranges: 3 to 55 years, and 12 to 58 years). Walking difficulty was the first symptom commonly reported. Neurological examination found distal muscle weakness and wasting with sensory loss, reduced tendon reflexes, and skeletal deformities. In addition, some patients presented with ataxic gait associated with incoordination that are not in the forefront of CMT features. NCS was consistent with the axonal pattern in three families. Genetic analysis revealed rare pathogenic variants in <i>BSCL2</i>, <i>SH3TC2</i>, and <i>PEX10</i>, and of unknown significance in <i>BAG3</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>This study reports rare variants in these CMT genes for the first time in SSA populations, expanding the global epidemiological, clinical, and genetic spectrum of these diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9081,"journal":{"name":"Brain and Behavior","volume":"15 5","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brb3.70496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905277","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}