A role for astrocytic miR-129-5p in frontotemporal dementia
Abstract Frontotemporal dementia is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe degeneration, resulting in behavioral changes, language difficulties, and cognitive decline. In this study, smallRNA sequencing was conducted on postmortem brain tissues obtained...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-025-03338-y |
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| author | Lalit Kaurani Ranjit Pradhan Sophie Schröder Susanne Burkhardt Anna-Lena Schuetz Dennis M. Krüger Tonatiuh Pena Peter Heutink Farahnaz Sananbenesi Andre Fischer |
| author_facet | Lalit Kaurani Ranjit Pradhan Sophie Schröder Susanne Burkhardt Anna-Lena Schuetz Dennis M. Krüger Tonatiuh Pena Peter Heutink Farahnaz Sananbenesi Andre Fischer |
| author_sort | Lalit Kaurani |
| collection | DOAJ |
| description | Abstract Frontotemporal dementia is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe degeneration, resulting in behavioral changes, language difficulties, and cognitive decline. In this study, smallRNA sequencing was conducted on postmortem brain tissues obtained from the frontal and temporal of FTD patients with GRN, MAPT, or C9ORF72 mutations. Our analysis identified miR-129-5p as consistently deregulated across all analyzed mutation conditions and brain regions. Functional investigations in in-vitro models revealed a novel role of miR-129-5p in astrocytes, where its loss led to neuroinflammation and impaired neuronal support functions, including reduced glutamate uptake. Depletion of miR-129-5p in astrocytes also resulted in the loss of neuronal spines and altered neuronal network activity in a cell culture system. These findings highlight miR-129-5p as a potential therapeutic target in neurodegenerative diseases and also sheds light on the role of astrocytes in Frontotemporal dementia pathogenesis. |
| format | Article |
| id | doaj-art-7c3bf11079414cb48b8fd5e1a4e4232d |
| institution | DOAJ |
| issn | 2158-3188 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj-art-7c3bf11079414cb48b8fd5e1a4e4232d2025-08-20T03:10:16ZengNature Publishing GroupTranslational Psychiatry2158-31882025-04-0115111410.1038/s41398-025-03338-yA role for astrocytic miR-129-5p in frontotemporal dementiaLalit Kaurani0Ranjit Pradhan1Sophie Schröder2Susanne Burkhardt3Anna-Lena Schuetz4Dennis M. Krüger5Tonatiuh Pena6Peter Heutink7Farahnaz Sananbenesi8Andre Fischer9Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)Research Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative DiseasesDepartment for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)Department for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)German Center for Neurodegenerative DiseasesResearch Group for Genome Dynamics in Brain Diseases, German Center for Neurodegenerative DiseasesDepartment for Systems Medicine and Epigenetics, German Center for Neurodegenerative Diseases (DZNE)Abstract Frontotemporal dementia is a debilitating neurodegenerative disorder characterized by frontal and temporal lobe degeneration, resulting in behavioral changes, language difficulties, and cognitive decline. In this study, smallRNA sequencing was conducted on postmortem brain tissues obtained from the frontal and temporal of FTD patients with GRN, MAPT, or C9ORF72 mutations. Our analysis identified miR-129-5p as consistently deregulated across all analyzed mutation conditions and brain regions. Functional investigations in in-vitro models revealed a novel role of miR-129-5p in astrocytes, where its loss led to neuroinflammation and impaired neuronal support functions, including reduced glutamate uptake. Depletion of miR-129-5p in astrocytes also resulted in the loss of neuronal spines and altered neuronal network activity in a cell culture system. These findings highlight miR-129-5p as a potential therapeutic target in neurodegenerative diseases and also sheds light on the role of astrocytes in Frontotemporal dementia pathogenesis.https://doi.org/10.1038/s41398-025-03338-y |
| spellingShingle | Lalit Kaurani Ranjit Pradhan Sophie Schröder Susanne Burkhardt Anna-Lena Schuetz Dennis M. Krüger Tonatiuh Pena Peter Heutink Farahnaz Sananbenesi Andre Fischer A role for astrocytic miR-129-5p in frontotemporal dementia Translational Psychiatry |
| title | A role for astrocytic miR-129-5p in frontotemporal dementia |
| title_full | A role for astrocytic miR-129-5p in frontotemporal dementia |
| title_fullStr | A role for astrocytic miR-129-5p in frontotemporal dementia |
| title_full_unstemmed | A role for astrocytic miR-129-5p in frontotemporal dementia |
| title_short | A role for astrocytic miR-129-5p in frontotemporal dementia |
| title_sort | role for astrocytic mir 129 5p in frontotemporal dementia |
| url | https://doi.org/10.1038/s41398-025-03338-y |
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