Molecular Neurobiology最新文献_第2页

Untargeted Metabolomics Revealed that Quercetin Inhibited Ferroptosis by Improving Metabolic Disorder in the Hippocampus of Perimenopausal Depression Model Rats. 非靶向代谢组学揭示槲皮素可通过改善围绝经期抑郁模型大鼠海马区的代谢紊乱抑制铁蛋白沉积

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-24 DOI: 10.1007/s12035-024-04445-5

Yali Hou, Heng Qian, Ranqi Yao, Ziran Yu, Jing Wang, Jiaohua Dai, Wenqi Cui, Jian Li, Xiujuan Zhao

{"title":"Untargeted Metabolomics Revealed that Quercetin Inhibited Ferroptosis by Improving Metabolic Disorder in the Hippocampus of Perimenopausal Depression Model Rats.","authors":"Yali Hou, Heng Qian, Ranqi Yao, Ziran Yu, Jing Wang, Jiaohua Dai, Wenqi Cui, Jian Li, Xiujuan Zhao","doi":"10.1007/s12035-024-04445-5","DOIUrl":"10.1007/s12035-024-04445-5","url":null,"abstract":"Perimenopausal depression is often accompanied by metabolic disorders, which have long-term harmful effects on women's physical and mental health. Quercetin, a kind of phytoestrogen, has anti-inflammatory, antioxidant, and nerve-protective effects, and can regulate various metabolic disorders. This study aims to investigate the effect of quercetin on hippocampal metabolic disorder in perimenopausal depression rat models based on untargeted metabolomics technology. The rat model of perimenopausal depression was established by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Rats with no difference in sucrose preference were randomly divided into four groups (n = 12): sham group, OVX-CUMS group (model group), model plus quercetin group, and model plus 17β-estradiol group. At the end of the experiment, hippocampal tissues were collected for untargeted metabolomics analysis, morphological analysis, and detection of related indicators. Metabolomics identified 23 differential metabolites in the model group, and the pathway analysis discovered hippocampus metabolic abnormalities including the metabolism of arachidonic acid metabolism, glycerophospholipid metabolism, and ubiquinone biosynthesis, accompanied by an increase in oxidative stress, inflammation, and lipid peroxidation indicators. At the same time, the morphological characteristics of ferroptosis occurred in the hippocampus in the model group. These abnormal changes were reversed by treatment with quercetin or 17β-estradiol. Quercetin can improve perimenopausal depression by regulating hippocampal metabolic disorders and reducing hippocampal ferroptosis in rats. These findings provide a new strategy for the use of quercetin in the prevention and treatment of perimenopausal depression.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2872-2888"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

tubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model. tubg1 体细胞突变体在斑马鱼模型中显示出与管蛋白病相关的神经发育表型

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-31 DOI: 10.1007/s12035-024-04448-2

Ozge Cark, Esra Katkat, Ipek Aydogdu, Evin Iscan, Yavuz Oktay, Gunes Ozhan

{"title":"tubg1 Somatic Mutants Show Tubulinopathy-Associated Neurodevelopmental Phenotypes in a Zebrafish Model.","authors":"Ozge Cark, Esra Katkat, Ipek Aydogdu, Evin Iscan, Yavuz Oktay, Gunes Ozhan","doi":"10.1007/s12035-024-04448-2","DOIUrl":"10.1007/s12035-024-04448-2","url":null,"abstract":"Development of the multilayered cerebral cortex relies on precise orchestration of neurogenesis, neuronal migration, and differentiation, processes tightly regulated by microtubule dynamics. Mutations in tubulin superfamily genes have been associated with tubulinopathies, encompassing a spectrum of cortical malformations including microcephaly and lissencephaly. Here, we focus on γ-tubulin, a pivotal regulator of microtubule nucleation encoded by TUBG1. We investigate its role in brain development using a zebrafish model with somatic tubg1 mutation, recapitulating features of TUBG1-associated tubulinopathies in patients and mouse disease models. We demonstrate that γ-tubulin deficiency disrupts neurogenesis and brain development, mirroring microcephaly phenotypes. Furthermore, we uncover a novel potential regulatory link between γ-tubulin and canonical Wnt/β-catenin signaling, with γ-tubulin deficiency impairing Wnt activity. Our findings provide insights into the pathogenesis of cortical defects and suggest that γ-tubulin could be a potential target for further research in neurodevelopmental disorders, although challenges such as mode of action, specificity, and potential side effects must be addressed.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3024-3039"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Curculigoside Regulates Apoptosis and Oxidative Stress Against Spinal Cord Injury by Modulating the Nrf-2/NQO-1 Signaling Pathway In Vitro and In Vivo. 莪术苷通过调节体外和体内Nrf-2/NQO-1信号通路调节脊髓损伤的细胞凋亡和氧化应激

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-04 DOI: 10.1007/s12035-024-04409-9

Yu Hou, Chaolun Liang, Lili Sui, Yang Li, Kai Wang, Xing Li, Kunrui Zheng, Haitao Su, Dianweng Xie, Dingkun Lin, Da Guo, Le Wang

{"title":"Curculigoside Regulates Apoptosis and Oxidative Stress Against Spinal Cord Injury by Modulating the Nrf-2/NQO-1 Signaling Pathway In Vitro and In Vivo.","authors":"Yu Hou, Chaolun Liang, Lili Sui, Yang Li, Kai Wang, Xing Li, Kunrui Zheng, Haitao Su, Dianweng Xie, Dingkun Lin, Da Guo, Le Wang","doi":"10.1007/s12035-024-04409-9","DOIUrl":"10.1007/s12035-024-04409-9","url":null,"abstract":"Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3082-3097"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Use of Identified Hypoxia-related Genes to Generate Models for Predicting the Prognosis of Cerebral Ischemia‒reperfusion Injury and Developing Treatment Strategies. 利用已识别的缺氧相关基因生成模型，以预测脑缺血再灌注损伤的预后并制定治疗策略。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-04 DOI: 10.1007/s12035-024-04433-9

Kaiwen Sun, Hongwei Li, Yang Dong, Lei Cao, Dongpeng Li, Jinghong Li, Manxia Zhang, Dongming Yan, Bo Yang

{"title":"The Use of Identified Hypoxia-related Genes to Generate Models for Predicting the Prognosis of Cerebral Ischemia‒reperfusion Injury and Developing Treatment Strategies.","authors":"Kaiwen Sun, Hongwei Li, Yang Dong, Lei Cao, Dongpeng Li, Jinghong Li, Manxia Zhang, Dongming Yan, Bo Yang","doi":"10.1007/s12035-024-04433-9","DOIUrl":"10.1007/s12035-024-04433-9","url":null,"abstract":"Cerebral ischemia‒reperfusion injury (CIRI) is a type of secondary brain damage caused by reperfusion after ischemic stroke due to vascular obstruction. In this study, a CIRI diagnostic model was established by identifying hypoxia-related differentially expressed genes (HRDEGs) in patients with CIRI. The ischemia‒reperfusion injury (IRI)-related datasets were downloaded from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ), and hypoxia-related genes in the Gene Cards database were identified. After the datasets were combined, hypoxia-related differentially expressed genes (HRDEGs) expressed in CIRI patients were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the HRDEGs were performed using online tools. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed with the combined gene dataset. CIRI diagnostic models based on HRDEGs were constructed via least absolute shrinkage and selection operator (LASSO) regression analysis and a support vector machine (SVM) algorithm. The efficacy of the 9 identified hub genes for CIRI diagnosis was evaluated via mRNA‒microRNA (miRNA) interaction, mRNA-RNA-binding protein (RBP) network interaction, immune cell infiltration, and receiver operating characteristic (ROC) curve analyses. We then performed logistic regression analysis and constructed logistic regression models based on the expression of the 9 HRDEGs. We next established a nomogram and calibrated the prediction data. Finally, the clinical utility of the constructed logistic regression model was evaluated via decision curve analysis (DCA). This study revealed 9 critical genes with high diagnostic value, offering new insights into the diagnosis and selection of therapeutic targets for patients with CIRI. : Not applicable.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3098-3124"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective. 精神分裂症患者血清外泌体脂质代谢失调：从生物标志物角度看精神分裂症

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-23 DOI: 10.1007/s12035-024-04477-x

Chen-Xi Xu, Wei Huang, Xiao-Jie Shi, Yang Du, Jia-Quan Liang, Xuan Fang, He-Yuan Chen, Yong Cheng

{"title":"Dysregulation of Serum Exosomal Lipid Metabolism in Schizophrenia: A Biomarker Perspective.","authors":"Chen-Xi Xu, Wei Huang, Xiao-Jie Shi, Yang Du, Jia-Quan Liang, Xuan Fang, He-Yuan Chen, Yong Cheng","doi":"10.1007/s12035-024-04477-x","DOIUrl":"10.1007/s12035-024-04477-x","url":null,"abstract":"Exosomes, crucial extracellular vesicles, have emerged as potential biomarkers for neurological conditions, including schizophrenia (SCZ). However, the exploration of exosomal lipids in the context of SCZ remains scarce, necessitating in-depth investigation. Leveraging ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), this study aimed to characterize the lipidomic profile of serum exosomes from SCZ patients, assessing their potential as novel biomarkers for SCZ diagnosis through absolute quantitative lipidomics. Our comprehensive lipidomic analysis unveiled 39 serum exosomal lipids that were differentially expressed between SCZ patients (n = 20) and healthy controls (HC, n = 20). These findings revealed a profound dysregulation in lipid metabolism pathways, notably in sphingolipid metabolism, glycerophospholipid metabolism, and linoleic acid metabolism. Among these, seven exosomal lipids stood out for their diagnostic potential, exhibiting remarkable ability to differentiate SCZ patients from HCs with an unparalleled classification performance, evidenced by an area under the curve (AUC) of 0.94 (95% CI, 0.82-1.00). These lipids included specific ceramides and phosphoethanolamines, pointing to a distinct lipid metabolic fingerprint associated with SCZ. Furthermore, bioinformatic analyses reinforced the pivotal involvement of these lipids in SCZ-related lipid metabolic processes, suggesting their integral role in the disorder's pathophysiology. This study significantly advances our understanding of SCZ by pinpointing dysregulated exosomal lipid metabolism as a key factor in its pathology. The identified serum exosome-derived lipids emerge as compelling biomarkers for SCZ diagnosis, offering a promising avenue towards the development of objective and reliable diagnostic tools.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3556-3567"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antioxidant Effect of Naringin Demonstrated Through a Bayes' Theorem Driven Multidisciplinary Approach Reveals its Prophylactic Potential as a Dietary Supplement for Ischemic Stroke. 贝叶斯定理驱动的多学科方法证明柚皮苷的抗氧化作用，揭示其作为缺血性中风膳食补充剂的预防潜力

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-10-01 DOI: 10.1007/s12035-024-04525-6

Manju Babu, Rajas M Rao, Anju Babu, Jenat Pazheparambil Jerom, Anaekshi Gogoi, Nikhil Singh, Meenakshi Seshadri, Animikh Ray, Bhaskara P Shelley, Arnab Datta

{"title":"Antioxidant Effect of Naringin Demonstrated Through a Bayes' Theorem Driven Multidisciplinary Approach Reveals its Prophylactic Potential as a Dietary Supplement for Ischemic Stroke.","authors":"Manju Babu, Rajas M Rao, Anju Babu, Jenat Pazheparambil Jerom, Anaekshi Gogoi, Nikhil Singh, Meenakshi Seshadri, Animikh Ray, Bhaskara P Shelley, Arnab Datta","doi":"10.1007/s12035-024-04525-6","DOIUrl":"10.1007/s12035-024-04525-6","url":null,"abstract":"Naringin (NAR), a flavanone glycoside, occurs widely in citrus fruits, vegetables, and alcoholic beverages. Despite evidence of the neuroprotective effects of NAR on animal models of ischemic stroke, brain cell-type-specific data about the antioxidant efficacy of NAR and possible protein targets of such beneficial effects are limited. Here, we demonstrate the brain cell type-specific prophylactic role of NAR, an FDA-listed food additive, in an in vitro oxygen-glucose deprivation (OGD) model of cerebral ischemia using MTT and DCFDA assays. Using Bayes' theorem-based predictive model, we first ranked the top-10 protein targets (ALDH2, ACAT1, CTSB, FASN, LDHA, PTGS1, CTSD, LGALS1, TARDBP, and CDK1) from a curated list of 289 NAR-interacting proteins in neurons that might be mediating its antioxidant effect in the OGD model. When preincubated with NAR for 2 days, N2a and CTX-TNA2 cells could withstand up to 8 h of OGD without a noticeable decrease in cell viability. This cerebroprotective effect is partly mediated by reducing intracellular ROS production in the above two brain cell types. The antioxidant effect of NAR was comparable with the equimolar (50 µM) concentration of clinically used ROS-scavenger and neuroprotective edaravone. Molecular docking of NAR with the top-10 protein targets from Bayes' analysis showed the lowest binding energy for CDK1 (- 8.8 kcal/M). Molecular dynamics simulation analysis showed that NAR acts by inhibiting CDK1 by stably occupying its ATP-binding cavity. Considering diet has been listed as a risk factor for stroke, NAR may be explored as a component of functional food for stroke or related neurological disorders.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3918-3933"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing Stroke Recurrence Risk by Using a Lipoprotein-Associated Phospholipase A2 and Platelet Count-Based Nomogram. 使用基于脂蛋白相关磷脂酶 A2 和血小板计数的提名图评估中风复发风险。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-23 DOI: 10.1007/s12035-024-04439-3

Yanlong Zhou, Yu Feng, Ning Xin, Jun Lu, Xingshun Xu

{"title":"Assessing Stroke Recurrence Risk by Using a Lipoprotein-Associated Phospholipase A2 and Platelet Count-Based Nomogram.","authors":"Yanlong Zhou, Yu Feng, Ning Xin, Jun Lu, Xingshun Xu","doi":"10.1007/s12035-024-04439-3","DOIUrl":"10.1007/s12035-024-04439-3","url":null,"abstract":"Stroke recurrence remains a critical challenge in clinical neurology, necessitating the identification of reliable predictive markers for better management and treatment strategies. This study investigates the interaction between lipoprotein-associated phospholipase A2 (Lp-PLA2) and platelets as a potential predictor for stroke recurrence, aiming to refine risk assessment and therapeutic approaches. In a retrospective cohort of 580 ischemic stroke patients, we analyzed clinical data with a focus on Lp-PLA2 and platelet levels. By using multivariable logistic regression, we identified independent predictors of stroke recurrence. These predictors were then used to develop a comprehensive nomogram. The study established diabetes mellitus, hypertension, low-density lipoprotein (LDL), Lp-PLA2 levels, and platelet counts as independent predictors of stroke recurrence. Crucially, the interaction parameter Lp-PLA2 * platelet (multiplication of Lp-PLA2 and platelet count) exhibited superior predictive power over each factor considered separately. Our nomogram incorporated diabetes mellitus, cerebral infarction causes, hypertension, LDL, and the Lp-PLA2 * platelet count interaction and demonstrated enhanced accuracy in predicting stroke recurrence compared to traditional risk models. The interaction between Lp-PLA2 and platelets emerged as a significant predictor for stroke recurrence when integrated with traditional risk factors. The developed nomogram offers a novel and practical tool in molecular neurobiology for assessing individual risks, facilitating personalized treatment strategies. This approach underscores the importance of multifactorial assessment in stroke management and opens avenues for targeted interventions to mitigate recurrence risks.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2835-2845"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation. 电针通过Foxp3乙酰化调控促进缺血性脑卒中后肠道Treg细胞的生成

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-25 DOI: 10.1007/s12035-024-04500-1

Yonglin Chen, Ling Ouyang, Xinyi Yang, Bufan Wu, Lingling Meng, Jialin Gu, Yaling Wang, Juan Li, Jingjing Zhang, Xinyue Jing, Shengfeng Lu, Lanying Liu, Shuping Fu

{"title":"Electroacupuncture Promotes the Generation of Intestinal Treg Cells After Ischemic Stroke by Foxp3 Acetylation Regulation.","authors":"Yonglin Chen, Ling Ouyang, Xinyi Yang, Bufan Wu, Lingling Meng, Jialin Gu, Yaling Wang, Juan Li, Jingjing Zhang, Xinyue Jing, Shengfeng Lu, Lanying Liu, Shuping Fu","doi":"10.1007/s12035-024-04500-1","DOIUrl":"10.1007/s12035-024-04500-1","url":null,"abstract":"Electroacupuncture (EA) has been shown to ameliorate brain injury and protect against intestinal injury after ischemic stroke. These protective effects are closely associated with the enhancement of regulatory T (Treg) cell numbers and function in the intestine, as well as the inhibition of intestinal γδ T cell production and their migration to the brain. This study aimed to elucidate the potential mechanism by which EA regulates intestinal Treg cell differentiation after stroke. Sprague-Dawley rats were divided into three groups: the sham group, the middle cerebral artery occlusion (MCAO) group, and the MCAO plus EA (MEA) group. The MCAO model was generated by occluding the middle cerebral artery. EA was applied to Baihui (GV20) acupoint once daily. Samples were collected 3 days after reperfusion. Our results showed that EA reduced the inflammatory response in the brain and intestine after ischemic stroke. EA treatment increased the percentage of Treg cells in the small intestine of rats. EA increased the levels of SCFAs, while also inhibiting histone deacetylase activity (HDAC). Additionally, acetylated Foxp3 protein in the small intestine was increased after EA treatment. These results suggest that EA at GV20 alleviates brain and intestinal inflammatory injury in stroke rats, potentially through the enhancement of SCFA-mediated Foxp3 acetylation in Treg cells.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3697-3711"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gut Microbiota Mediates Neuroinflammation in Alzheimer's Disease: Unraveling Key Factors and Mechanistic Insights. 肠道微生物群介导阿尔茨海默病的神经炎症：揭示关键因素和机理。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-25 DOI: 10.1007/s12035-024-04513-w

Liang Junyi, Wang Yueyang, Liu Bin, Dong Xiaohong, Cai Wenhui, Zhang Ning, Zhang Hong

引用次数: 0

Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization. 通过线粒体相关全基因组孟德尔随机化鉴定神经退行性疾病的潜在致病基因。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-30 DOI: 10.1007/s12035-024-04528-3

Kang-Fu Yin, Ting Chen, Xiao-Jing Gu, Zheng Jiang, Wei-Ming Su, Qing-Qing Duan, Xiang-Jin Wen, Bei Cao, Ju-Rong Li, Li-Yi Chi, Yong-Ping Chen

{"title":"Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.","authors":"Kang-Fu Yin, Ting Chen, Xiao-Jing Gu, Zheng Jiang, Wei-Ming Su, Qing-Qing Duan, Xiang-Jin Wen, Bei Cao, Ju-Rong Li, Li-Yi Chi, Yong-Ping Chen","doi":"10.1007/s12035-024-04528-3","DOIUrl":"10.1007/s12035-024-04528-3","url":null,"abstract":"Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3892-3902"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0