Chenyang Wang, Xiaolu Bu, Mengyao Cao, Yunyu Lian, Haocong Ling, Mo You, Junfei Yi, Xiaoya Gao, Duobin Wu, Yang Li
{"title":"Mir-199a-3p通过促进M1极化小胶质细胞Mir-199a-3p M1,加重阿尔茨海默病转基因小鼠模型中的神经炎症。","authors":"Chenyang Wang, Xiaolu Bu, Mengyao Cao, Yunyu Lian, Haocong Ling, Mo You, Junfei Yi, Xiaoya Gao, Duobin Wu, Yang Li","doi":"10.1186/s12868-025-00965-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chronic neuroinflammation, driven by M1-polarized microglia, is a core pathological mechanism of Alzheimer's disease (AD). Elevated expression levels of miR-199a-3p and pro-inflammatory cytokines were detected in the hippocampi of AD transgenic mice and in LPS-stimulated BV2 microglial cells. We hypothesized that miR-199a-3p exacerbates neuroinflammation by promoting M1 microglial polarization in AD progression. M1 (AD) 。 AD LPS BV2 miR-199a-3p 。 miR-199a-3p AD M1 。 OBJECTIVE: To explore the role of miR-199a-3p in AD-associated neuroinflammation. miR-199a-3p AD 。 METHODS: AD transgenic (APPswe/PSEN1dE9) mice and LPS-treated BV2 cells were used to assess miR-199a-3p effects in vivo and in vitro. Inflammatory cytokines and markers for microglial cell typing were detected. Transcriptome sequencing was performed on miR-199a-3p-modulated BV2 cells, and the sequencing data were cross-analyzed with public databases to predict miR-199a-3p-mediated pathways.AD (APPswe/PSEN1dE9) LPS BV2 miR-199a-3p 。。 miR-199a-3p BV2 ,, miR-199a-3p 。 RESULTS: Intracerebroventricular administration of miR-199a-3p agomir exacerbated amyloid deposition and impaired cognitive function in AD mice, and promoted microglial polarization toward the M1 phenotype. Conversely, treatment with miR-199a-3p antagomir attenuated AD pathology and suppressed M1 polarization. In LPS treated BV2 cells, miR-199a-3p mimics promoted M1 polarization, while inhibitors reversed this effect. Transcriptome analysis revealed that miR-199a-3p downregulated WDR76, subsequently suppressing cell cycle-associated pathways, IL-17 signaling, and FOXO pathways, resulting in an increase in the proportion of M1 type microglia. miR-199a-3p agomir AD , M1 。, miR-199a-3p AD M1 。 LPS BV2 ,miR-199a-3p M1 ,。,miR-199a-3p WDR76,、 IL-17 FOXO , M1 。 CONCLUSION: MiR-199a-3p aggravates neuroinflammation of AD by promoting M1-polarization microglia. These findings highlight miR-199a-3p as a potential therapeutic target for AD.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"45"},"PeriodicalIF":2.4000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mir-199a-3p aggravates neuroinflammation in an Alzheimer's disease transgenic mouse model by promoting M1-polarization microgliaMir-199a-3p M1.\",\"authors\":\"Chenyang Wang, Xiaolu Bu, Mengyao Cao, Yunyu Lian, Haocong Ling, Mo You, Junfei Yi, Xiaoya Gao, Duobin Wu, Yang Li\",\"doi\":\"10.1186/s12868-025-00965-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Chronic neuroinflammation, driven by M1-polarized microglia, is a core pathological mechanism of Alzheimer's disease (AD). Elevated expression levels of miR-199a-3p and pro-inflammatory cytokines were detected in the hippocampi of AD transgenic mice and in LPS-stimulated BV2 microglial cells. We hypothesized that miR-199a-3p exacerbates neuroinflammation by promoting M1 microglial polarization in AD progression. M1 (AD) 。 AD LPS BV2 miR-199a-3p 。 miR-199a-3p AD M1 。 OBJECTIVE: To explore the role of miR-199a-3p in AD-associated neuroinflammation. miR-199a-3p AD 。 METHODS: AD transgenic (APPswe/PSEN1dE9) mice and LPS-treated BV2 cells were used to assess miR-199a-3p effects in vivo and in vitro. Inflammatory cytokines and markers for microglial cell typing were detected. Transcriptome sequencing was performed on miR-199a-3p-modulated BV2 cells, and the sequencing data were cross-analyzed with public databases to predict miR-199a-3p-mediated pathways.AD (APPswe/PSEN1dE9) LPS BV2 miR-199a-3p 。。 miR-199a-3p BV2 ,, miR-199a-3p 。 RESULTS: Intracerebroventricular administration of miR-199a-3p agomir exacerbated amyloid deposition and impaired cognitive function in AD mice, and promoted microglial polarization toward the M1 phenotype. Conversely, treatment with miR-199a-3p antagomir attenuated AD pathology and suppressed M1 polarization. In LPS treated BV2 cells, miR-199a-3p mimics promoted M1 polarization, while inhibitors reversed this effect. Transcriptome analysis revealed that miR-199a-3p downregulated WDR76, subsequently suppressing cell cycle-associated pathways, IL-17 signaling, and FOXO pathways, resulting in an increase in the proportion of M1 type microglia. miR-199a-3p agomir AD , M1 。, miR-199a-3p AD M1 。 LPS BV2 ,miR-199a-3p M1 ,。,miR-199a-3p WDR76,、 IL-17 FOXO , M1 。 CONCLUSION: MiR-199a-3p aggravates neuroinflammation of AD by promoting M1-polarization microglia. These findings highlight miR-199a-3p as a potential therapeutic target for AD.</p>\",\"PeriodicalId\":9031,\"journal\":{\"name\":\"BMC Neuroscience\",\"volume\":\"26 1\",\"pages\":\"45\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"BMC Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12868-025-00965-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12868-025-00965-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Mir-199a-3p aggravates neuroinflammation in an Alzheimer's disease transgenic mouse model by promoting M1-polarization microgliaMir-199a-3p M1.
Background: Chronic neuroinflammation, driven by M1-polarized microglia, is a core pathological mechanism of Alzheimer's disease (AD). Elevated expression levels of miR-199a-3p and pro-inflammatory cytokines were detected in the hippocampi of AD transgenic mice and in LPS-stimulated BV2 microglial cells. We hypothesized that miR-199a-3p exacerbates neuroinflammation by promoting M1 microglial polarization in AD progression. M1 (AD) 。 AD LPS BV2 miR-199a-3p 。 miR-199a-3p AD M1 。 OBJECTIVE: To explore the role of miR-199a-3p in AD-associated neuroinflammation. miR-199a-3p AD 。 METHODS: AD transgenic (APPswe/PSEN1dE9) mice and LPS-treated BV2 cells were used to assess miR-199a-3p effects in vivo and in vitro. Inflammatory cytokines and markers for microglial cell typing were detected. Transcriptome sequencing was performed on miR-199a-3p-modulated BV2 cells, and the sequencing data were cross-analyzed with public databases to predict miR-199a-3p-mediated pathways.AD (APPswe/PSEN1dE9) LPS BV2 miR-199a-3p 。。 miR-199a-3p BV2 ,, miR-199a-3p 。 RESULTS: Intracerebroventricular administration of miR-199a-3p agomir exacerbated amyloid deposition and impaired cognitive function in AD mice, and promoted microglial polarization toward the M1 phenotype. Conversely, treatment with miR-199a-3p antagomir attenuated AD pathology and suppressed M1 polarization. In LPS treated BV2 cells, miR-199a-3p mimics promoted M1 polarization, while inhibitors reversed this effect. Transcriptome analysis revealed that miR-199a-3p downregulated WDR76, subsequently suppressing cell cycle-associated pathways, IL-17 signaling, and FOXO pathways, resulting in an increase in the proportion of M1 type microglia. miR-199a-3p agomir AD , M1 。, miR-199a-3p AD M1 。 LPS BV2 ,miR-199a-3p M1 ,。,miR-199a-3p WDR76,、 IL-17 FOXO , M1 。 CONCLUSION: MiR-199a-3p aggravates neuroinflammation of AD by promoting M1-polarization microglia. These findings highlight miR-199a-3p as a potential therapeutic target for AD.
期刊介绍:
BMC Neuroscience is an open access, peer-reviewed journal that considers articles on all aspects of neuroscience, welcoming studies that provide insight into the molecular, cellular, developmental, genetic and genomic, systems, network, cognitive and behavioral aspects of nervous system function in both health and disease. Both experimental and theoretical studies are within scope, as are studies that describe methodological approaches to monitoring or manipulating nervous system function.