Molecular Neurobiology最新文献

{"title":"Exosomes from Hypoxia-treated Mesenchymal Stem Cells: Promoting Neuroprotection in Ischemic Stroke Through miR-214-3p/PTEN Mechanism.","authors":"Qian Wu, Jia-Huan Wu, Zhi-Yuan Ye, Wen She, Wen-Jie Peng, Hui-Xin Zhang, Cui Qi, Tian Tian, Xiao-Yu Hou, Jun Gao","doi":"10.1007/s12035-024-04056-0","DOIUrl":"10.1007/s12035-024-04056-0","url":null,"abstract":"<p><p>Stroke stands as the second leading cause of death globally, surpassed only by ischemic heart disease. It accounts for 9% of total worldwide deaths. Given the swiftly evolving landscape, medical professionals and researchers are devoting increased attention to identifying more effective and safer treatments. Recent years have witnessed a focus on exosomes derived from mesenchymal stem cells cultivated under hypoxic conditions, referred to as Hypo-Exo. These specialized exosomes contain an abundance of components that facilitate the restoration of ischemic tissue, surpassing the content found in normal exosomes. Despite advancements, the precise role of Hypo-Exo in cases of cerebral ischemia remains enigmatic. Therefore, this study was designed to shed light on the potential efficacy of Hypo-Exo in stroke treatment. Our investigations unveiled promising outcomes, as the administration of Hypo-Exo led to improved behavioral deficits and reduced infarct areas in mice affected by ischemic conditions. Notably, these positive effects were hindered when Hypo-Exo loaded with anti-miR-214-3p were introduced, implying that the neuroprotective attributes of Hypo-Exo are reliant on miR-214-3p. This conclusion was substantiated by the high levels of miR-214-3p detected within Hypo-Exo. Furthermore, our examination of the ischemic penumbra zone revealed a gradual and sustained escalation in PTEN expression, a phenomenon effectively countered by Hypo-Exo treatment. Collectively, our findings suggest the existence of a regulatory pathway centered on miR-214-3p within Hypo-Exo. This pathway exerts a downregulating influence on the PTEN/Akt signaling pathway, thereby contributing to the amelioration of neurological function subsequent to ischemia-reperfusion events.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990628","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}

{"title":"Transcriptomics and Metabolomics Unveil the Neuroprotection Mechanism of AnGong NiuHuang (AGNH) Pill Against Ischaemic Stroke Injury.","authors":"Liangliang Tian, Guangzhao Cao, Xiaotong Zhu, Lihan Wang, Jingyi Hou, Yi Zhang, He Xu, Lixia Wang, Shicong Wang, Chen Zhao, Hongjun Yang, Jingjing Zhang","doi":"10.1007/s12035-024-04016-8","DOIUrl":"10.1007/s12035-024-04016-8","url":null,"abstract":"<p><p>As a famous prescription in China, AnGong NiuHuang (AGNH) pill exerts good neuroprotection for ischaemic stroke (IS), but its mechanism is still unclear. In this study, the neuroprotection of AGNH was evaluated in the rat IS model which were established with the surgery of middle cerebral artery occlusion (MCAO), and the potential mechanism was elucidated by transcriptomic analysis and metabolomic analysis. AGNH treatment obviously decreased the infarct volume and Zea-Longa 5-point neurological deficit scores, improved the survival percentage of rats, regional cerebral blood flow (rCBF), and rat activity distance and activity time. Transcriptomics showed that AGNH exerted its anti-inflammatory effects by affecting the regulatory network including Tyrobp, Syk, Tlr2, Myd88 and Ccl2 as the core. Integrating transcriptomics and metabolomics identified 8 key metabolites regulated by AGNH, including L-histidine, L-serine, L-alanine, fumaric acid, malic acid, and N-(L-arginino) succinate, 1-pyrroline-4-hydroxy-2-carboxylate and 1-methylhistamine in the rats with IS. Additionally, AGNH obviously reduced Tyrobp, Syk, Tlr2, Myd88 and Ccl2 at both the mRNA and protein levels, decreased IL-1β, KC-GRO, IL-13, TNF-α, cleaved caspase 3 and p65 nucleus translocation, but increased IκBα expression. Network pharmacology analysis showed that quercetin, beta-sitosterol, baicalein, naringenin, acacetin, berberine and palmatine may play an important role in protecting against IS. Taken together, this study reveals that AGNH reduced neuroinflammation and protected against IS by inhibiting Tyrobp/Syk and Tlr2/Myd88, as well as NF-κB signalling pathway and regulating multiple metabolites.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944330","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}

{"title":"IRAK-M Plays A Role in the Pathology of Amyotrophic Lateral Sclerosis Through Suppressing the Activation of Microglia.","authors":"Xinghua Zhong, Chuqiao Li, Yanran Li, Yingyi Huang, Jingsi Liu, Anqi Jiang, Jinyu Chen, Yu Peng","doi":"10.1007/s12035-024-04065-z","DOIUrl":"10.1007/s12035-024-04065-z","url":null,"abstract":"<p><p>Microglial activation plays a crucial role in the disease progression in amyotrophic lateral sclerosis (ALS). Interleukin receptor-associated kinases-M (IRAK-M) is an important negative regulatory factor in the Toll-like receptor 4 (TLR4) pathway during microglia activation, and its mechanism in this process is still unclear. In the present study, we aimed to investigate the dynamic changes of IRAK-M and its protective effects for motor neurons in SOD1-G93A mouse model of ALS. qPCR (Real-time Quantitative PCR Detecting System) were used to examine the mRNA levels of IRAK-M in the spinal cord in both SOD1-G93A mice and their age-matched wild type (WT) littermates at 60, 100 and 140 days of age. We established an adeno-associated virus 9 (AAV9)-based platform by which IRAK-M was targeted mostly to microglial cells to investigate whether this approach could provide a protection in the SOD1-G93A mouse. Compared with age-matched WT mice, IRAK-M mRNA level was elevated at 100 and 140 days in the anterior horn region of spinal cords in the SOD1-G93A mouse. AAV9-IRAK-M treated SOD1-G93A mice showed reduction of IL-1β mRNA levels and significant improvements in the numbers of spinal motor neurons in spinal cord. Mice also showed previously reduction of muscle atrophy. Our data revealed the dynamic changes of IRAK-M during ALS pathological progression and demonstrated that an AAV9-IRAK-M delivery was an effective and translatable therapeutic approach for ALS. These findings may help identify potential molecular targets for ALS therapy.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990629","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}

{"title":"High Systemic Inflammatory Protein Index Is Associated with Clinically Ineffective Reperfusion in Acute Anterior Circulation Ischemic Stroke Patients Undergoing Endovascular Treatment.","authors":"Mengxuan Xiao, Xiaolin Zhao, Jiaqi Luo, Zhiliang Zhu, Lihua Wei, Bingbing Li, Zhong Ji, Yongming Wu, Suyue Pan, Zhenzhou Lin, Kaibin Huang","doi":"10.1007/s12035-024-04068-w","DOIUrl":"10.1007/s12035-024-04068-w","url":null,"abstract":"<p><p>Nearly half of the patients undergoing endovascular treatment (EVT) do not have favorable outcomes despite successful recanalization of the occluded artery, which is also known as clinically ineffective reperfusion. We proposed a novel index-the systemic inflammatory protein index (SIPI), based on albumin, globulin, and C-reaction protein (CRP). We aimed to evaluate the relationship between inflammatory biomarkers at varying time points and the 90-day functional outcomes and investigate inflammatory biomarkers' dynamic changes during hospitalization in acute ischemic stroke (AIS) patients of anterior circulation undergoing EVT. We retrospectively recruited consecutive patients diagnosed with AIS of anterior circulation and treated with EVT from January 2018 to June 2022 in Nanfang Hospital. Albumin, globulin, and CRP were recorded on admission, 1 day, 3 days, and 7 days after EVT. An unfavorable functional outcome was defined as 90-day modified Rankin Scale (mRS) of 3-6. Albumin-to-globulin ratio (AGR), C-reactive protein-to-albumin ratio (CAR), and SIPI were calculated as follows: AGR = albumin/globulin; CAR = CRP/albumin; SIPI = CRP × globulin/albumin. A total of 238 consecutive anterior circulation AIS patients with EVT were included, among which 145 (60.9%) patients had unfavorable outcomes. After adjusting for confounding factors, admission globulin, admission AGR, 1-day AGR, 3-day albumin, 3-day CRP, 3-day CAR, 3-day SIPI, 7-day albumin, 7-day CRP, 7-day CAR, and 7-day SIPI showed an independent association with 90-day functional outcome. Of them, 3-day SIPI had the most robust discriminative ability with an area under the curve of 0.719 (CI 0.630-0.808, p < 0.001). There were differences in the dynamic change of inflammatory biomarkers between the subjects with favorable and unfavorable functional outcomes. Inflammatory biomarkers, including albumin, globulin, CRP, AGR, CAR, and SIPI, are independent predictors of 90-day unfavorable outcomes in anterior circulation AIS patients with EVT. SIPI of day 3 has the highest predictive value.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996827","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}

{"title":"Selective Medial Septum Lesions in Healthy Rats Induce Longitudinal Changes in Microstructure of Limbic Regions, Behavioral Alterations, and Increased Susceptibility to Status Epilepticus.","authors":"Hiram Luna-Munguia, Deisy Gasca-Martinez, Alejandra Garay-Cortes, Daniela Coutiño, Mirelta Regalado, Ericka de Los Rios, Paulina Villaseñor, Fernando Hidalgo-Flores, Karen Flores-Guapo, Brandon Yair Benito, Luis Concha","doi":"10.1007/s12035-024-04069-9","DOIUrl":"10.1007/s12035-024-04069-9","url":null,"abstract":"<p><p>Septo-hippocampal pathway, crucial for physiological functions and involved in epilepsy. Clinical monitoring during epileptogenesis is complicated. We aim to evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals' behavior and susceptibility to establishing a pilocarpine-induced status epilepticus. Male Sprague-Dawley rats were injected into the MS with vehicle or saporins (to deplete GABAergic or cholinergic neurons; n = 16 per group). Thirty-two animals were used for diffusion tensor imaging (DTI); scanned before surgery and 14 and 49 days post-injection. Fractional anisotropy and apparent diffusion coefficient were evaluated in the fimbria, dorsal hippocampus, ventral hippocampus, dorso-medial thalamus, and amygdala. Between scans 2 and 3, animals were submitted to diverse behavioral tasks. Stainings were used to analyze tissue alterations. Twenty-four different animals received pilocarpine to evaluate the latency and severity of the status epilepticus 2 weeks after surgery. Additionally, eight different animals were only used to evaluate the neuronal damage inflicted on the MS 1 week after the molecular surgery. Progressive changes in DTI parameters in both white and gray matter structures of the four evaluated groups were observed. Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Histologically, the GABAergic toxin also induced aberrant mossy fiber sprouting, tissue damage, and neuronal death. Regarding the pilocarpine-induced status epilepticus, this agent provoked an increased mortality rate. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Alpha-Synuclein Gene (SNCA) is a Genomic Target of Methyl-CpG Binding Protein 2 (MeCP2)-Implications for Parkinson's Disease and Rett Syndrome.","authors":"Ina Schmitt, Bernd O Evert, Amit Sharma, Hassan Khazneh, Chris Murgatroyd, Ullrich Wüllner","doi":"10.1007/s12035-024-03974-3","DOIUrl":"10.1007/s12035-024-03974-3","url":null,"abstract":"<p><p>Mounting evidence suggests a prominent role for alpha-synuclein (a-syn) in neuronal cell function. Alterations in the levels of cellular a-syn have been hypothesized to play a critical role in the development of Parkinson's disease (PD); however, mechanisms that control expression of the gene for a-syn (SNCA) in cis and trans as well as turnover of a-syn are not well understood. We analyzed whether methyl-CpG binding protein 2 (MeCP2), a protein that specifically binds methylated DNA, thus regulating transcription, binds at predicted binding sites in intron 1 of the SNCA gene and regulates a-syn protein expression. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility-shift assays (EMSA) were used to confirm binding of MeCP2 to regulatory regions of SNCA. Site-specific methylation and introduction of localized mutations by CRISPR/Cas9 were used to investigate the binding properties of MeCP2 in human SK-N-SH neuroblastoma cells. The significance of MeCP2 for SNCA regulation was further investigated by overexpressing MeCP2 and mutated variants of MeCP2 in MeCP2 knockout cells. We found that methylation-dependent binding of MeCP2 at a restricted region of intron 1 of SNCA had a significant impact on the production of a-syn. A single nucleotide substitution near to CpG1 strongly increased the binding of MeCP2 to intron 1 of SNCA and decreased a-syn protein expression by 60%. In contrast, deletion of a single nucleotide closed to CpG2 led to reduced binding of MeCP2 and significantly increased a-syn levels. In accordance, knockout of MeCP2 in SK-N-SH cells resulted in a significant increase in a-syn production, demonstrating that SNCA is a genomic target for MeCP2 regulation. In addition, the expression of two mutated MeCP2 variants found in Rett syndrome (RTT) showed a loss of their ability to reduce a-syn expression. This study demonstrates that methylation of CpGs and binding of MeCP2 to intron 1 of the SNCA gene plays an important role in the control of a-syn expression. In addition, the changes in SNCA regulation found by expression of MeCP2 variants carrying mutations found in RTT patients may be of importance for the elucidation of a new molecular pathway in RTT, a rare neurological disorder caused by mutations in MECP2.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"m6A/m1A/m5C-Associated Methylation Alterations and Immune Profile in MDD.","authors":"Xin Ren, Zhuxiao Feng, Xiaodong Ma, Lijuan Huo, Huiying Zhou, Ayu Bai, Shujie Feng, Ying Zhou, Xuchu Weng, Changhe Fan","doi":"10.1007/s12035-024-04042-6","DOIUrl":"10.1007/s12035-024-04042-6","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a prevalent psychiatric condition often accompanied by severe impairments in cognitive and functional capacities. This research was conducted to identify RNA modification-related gene signatures and associated functional pathways in MDD. Differentially expressed RNA modification-related genes in MDD were first identified. And a random forest model was developed and distinct RNA modification patterns were discerned based on signature genes. Then, comprehensive analyses of RNA modification-associated genes in MDD were performed, including functional analyses and immune cell infiltration. The study identified 29 differentially expressed RNA modification-related genes in MDD and two distinct RNA modification patterns. TRMT112, MBD3, NUDT21, and IGF2BP1 of the risk signature were detected. Functional analyses confirmed the involvement of RNA modification in pathways like phosphatidylinositol 3-kinase signaling and nucleotide oligomerization domain (NOD)-like receptor signaling in MDD. NUDT21 displayed a strong positive correlation with type 2 T helper cells, while IGF2BP1 negatively correlated with activated CD8 T cells, central memory CD4 T cells, and natural killer T cells. In summary, further research into the roles of NUDT21 and IGF2BP1 would be valuable for understanding MDD prognosis. The identified RNA modification-related gene signatures and pathways provide insights into MDD molecular etiology and potential diagnostic biomarkers.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140059921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pongamol Prevents Neurotoxicity via the Activation of MAPKs/Nrf2 Signaling Pathway in H₂O₂-Induced Neuronal PC12 Cells and Prolongs the Lifespan of Caenorhabditis elegans.","authors":"Shaojun Wu, Jie Miao, Susu Zhu, Xinyuan Wu, Jindan Shi, Jichao Zhou, Yi Xing, Kun Hu, Jie Ren, Hao Yang","doi":"10.1007/s12035-024-04110-x","DOIUrl":"10.1007/s12035-024-04110-x","url":null,"abstract":"<p><p>Despite tremendous advances in modern medicine, effective prevention or therapeutic strategies for age-related neurodegenerative diseases such as Alzheimer's disease (AD) remain limited. Growing evidence now suggests that oxidative stress and apoptosis are increasingly associated with AD as promising therapeutic targets. Pongamol, a flavonoid, is the main constituent of pongamia pinnata and possesses a variety of pharmacological activities such as antioxidant, anti-aging and anti-inflammatory. In the present study, we investigated the antioxidant effects and mechanisms of pongamol in H₂O₂-induced PC12 cells and Caenorhabditis elegans (C. elegans). Our findings revealed that pongamol reduced cellular damage and apoptosis in H₂O₂-induced PC12 cells. Furthermore, pongamol reduced levels of apoptosis-related proteins Bax, Cyto C, Cleaved Caspase-3, and Cleaved PARP1, and increased the level of anti-apoptotic protein Bcl-2. Pongamol also effectively attenuated the level of oxidative stress markers such as glutathione (GSH) and reactive oxygen species (ROS) in H₂O₂-induced PC12 cells. Additionally, pongamol possessed antioxidant activity in H₂O₂-induced PC12 cells through the MAPKs/Nrf2 signaling pathway. Furthermore, pongamol exerted neuroprotective and anti-aging effects in C. elegans. All together, these results suggested that pongamol has a potential neuroprotective effect through the modulation of MAPKs/Nrf2 signaling pathway.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131919","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}

{"title":"Effects of Bone Marrow Mesenchymal Stem Cell-Derived Exosomes in Central Nervous System Diseases.","authors":"Miao Chai, Gang Su, Wei Chen, Juan Gao, Qionghui Wu, Jinyang Song, Zhenchang Zhang","doi":"10.1007/s12035-024-04032-8","DOIUrl":"10.1007/s12035-024-04032-8","url":null,"abstract":"<p><p>Central nervous system (CNS) diseases are one of the diseases that threaten human health. The delivery of drugs targeting the CNS has always been a significant challenge; the blood-brain barrier (BBB) is the main obstacle that must be overcome. The rise of bone marrow mesenchymal stem cell (BMSC) therapy has brought hope for the treatment of CNS diseases. However, the problems of low homing rate, susceptibility differentiation into astrocytes, immune rejection, and formation of iatrogenic tumors of transplanted BMSCs limit their clinical application. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have become a hot research topic in the treatment of CNS diseases in recent years because of their excellent histocompatibility, low immunogenicity, ease of crossing the BBB, and their ability to serve as natural carriers for treatment. This article reviews the mechanisms of BMSC-Exos in CNS diseases and provides direction for further research.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932016","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}

{"title":"Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson's Disease: Implications for Gut Microbiota and PGC-1α.","authors":"Yuxuan Dong, Yueyan Qi, Jinhu Chen, Siyuan Han, Wenjing Su, Xin Ma, Yang Yu, Yanqin Wang","doi":"10.1007/s12035-024-04038-2","DOIUrl":"10.1007/s12035-024-04038-2","url":null,"abstract":"<p><p>Intestinal dysbiosis plays a critical role in the pathogenesis of Parkinson's disease (PD), and probiotics have emerged as potential modulators of central nervous system function through the microbiota-gut-brain axis. This study aimed to elucidate the anti-inflammatory effects and underlying mechanisms of the probiotic strain Bifidobacterium animalis subsp. lactis NJ241 (NJ241) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The impact of NJ241 was comprehensively assessed in PD mice through behavioral tests, immunofluorescence, Western blotting, enzyme-linked immunosorbent assay (ELISA), 16S rRNA sequencing, and short-chain fatty acid (SCFA) detection. NJ241 exhibited notable efficacy in mitigating MPTP-induced weight loss, gastrointestinal dysfunction, and behavioral deficits in mice. Furthermore, it demonstrated protected against MPTP-induced dopaminergic neuron death and inhibited the activation of glial cells in the substantia nigra (SN). NJ241 demonstrated the ability to normalized dysbiosis in the intestinal microbiota and elevate SCFA levels in PD mice. Additionally, NJ241 reversed MPTP-induced reductions in colonic GLP-1 levels and the expression of GLP-1R and PGC-1α in the SN. Notably, GLP-1R antagonists partially reversed the inhibitory effects of NJ241 on the activation of glial cells in the SN. In summary, NJ241 exerts a neuroprotective effect against MPTP-induced neuroinflammation by enhancing intestinal GLP-1 levels and activating nigral PGC-1α signaling. These findings provide a rationale for the exploration and development of probiotic-based therapeutic strategies for PD.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}