Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia
Abstract 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 micr...
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BMC
2025-07-01
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| Series: | BMC Neuroscience |
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| Online Access: | https://doi.org/10.1186/s12868-025-00965-5 |
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| author | Chenyang Wang Xiaolu Bu Mengyao Cao Yunyu Lian Haocong Ling Mo You Junfei Yi Xiaoya Gao Duobin Wu Yang Li |
| author_facet | Chenyang Wang Xiaolu Bu Mengyao Cao Yunyu Lian Haocong Ling Mo You Junfei Yi Xiaoya Gao Duobin Wu Yang Li |
| author_sort | Chenyang Wang |
| collection | DOAJ |
| description | Abstract 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. Objective To explore the role of miR-199a-3p in AD-associated neuroinflammation. 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. 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. 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. |
| format | Article |
| id | doaj-art-ae4bf0bd42e54e92aa4d57148c3ac5a6 |
| institution | Kabale University |
| issn | 1471-2202 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj-art-ae4bf0bd42e54e92aa4d57148c3ac5a62025-08-24T11:09:52ZengBMCBMC Neuroscience1471-22022025-07-0126111610.1186/s12868-025-00965-5Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microgliaChenyang Wang0Xiaolu Bu1Mengyao Cao2Yunyu Lian3Haocong Ling4Mo You5Junfei Yi6Xiaoya Gao7Duobin Wu8Yang Li9Department of Geriatrics, Zhujiang Hospital, Southern Medical UniversityThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical UniversityThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical UniversityThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical UniversityThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical UniversityThe Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Neurosurgery, Peking university first hospitalDepartment of Neurology, Zhujiang Hospital, Southern Medical UniversityDepartment of Geriatrics, Zhujiang Hospital, Southern Medical UniversityDepartment of Geriatrics, Zhujiang Hospital, Southern Medical UniversityAbstract 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. Objective To explore the role of miR-199a-3p in AD-associated neuroinflammation. 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. 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. 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.https://doi.org/10.1186/s12868-025-00965-5MiR-199a-3pAlzheimer’s diseaseNeuroinflammationMicroglia |
| spellingShingle | Chenyang Wang Xiaolu Bu Mengyao Cao Yunyu Lian Haocong Ling Mo You Junfei Yi Xiaoya Gao Duobin Wu Yang Li Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia BMC Neuroscience MiR-199a-3p Alzheimer’s disease Neuroinflammation Microglia |
| title | Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia |
| title_full | Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia |
| title_fullStr | Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia |
| title_full_unstemmed | Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia |
| title_short | Mir-199a-3p aggravates neuroinflammation in an Alzheimer’s disease transgenic mouse model by promoting M1-polarization microglia |
| title_sort | mir 199a 3p aggravates neuroinflammation in an alzheimer s disease transgenic mouse model by promoting m1 polarization microglia |
| topic | MiR-199a-3p Alzheimer’s disease Neuroinflammation Microglia |
| url | https://doi.org/10.1186/s12868-025-00965-5 |
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