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Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice
microRNA-29a (miR-29a) increases with age in humans and mice, and, in the brain, it has a role in neuronal maturation and response to inflammation. We previously associated higher miR-29a levels in human brain with faster antemortem cognitive decline, suggesting that lowering miR-29a levels could am...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462195/ https://www.ncbi.nlm.nih.gov/pubmed/37645711 http://dx.doi.org/10.21203/rs.3.rs-3235257/v1 |
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author | Mei, Zhen Liu, Jiaqi Schroeder, Jason P Weinshenker, David Duong, Duc M. Seyfried, Nicholas T. Li, Yujing Jin, Peng Wingo, Aliza P. Wingo, Thomas S. |
author_facet | Mei, Zhen Liu, Jiaqi Schroeder, Jason P Weinshenker, David Duong, Duc M. Seyfried, Nicholas T. Li, Yujing Jin, Peng Wingo, Aliza P. Wingo, Thomas S. |
author_sort | Mei, Zhen |
collection | PubMed |
description | microRNA-29a (miR-29a) increases with age in humans and mice, and, in the brain, it has a role in neuronal maturation and response to inflammation. We previously associated higher miR-29a levels in human brain with faster antemortem cognitive decline, suggesting that lowering miR-29a levels could ameliorate memory impairment in the 5xFAD AD mouse model. To test this hypothesis, we generated an adeno-associated virus (AAV) expressing GFP and a miR-29a “sponge” or empty vector. We found that the AAV expressing miR-29a sponge functionally reduced miR-29a levels, and improved measures of memory in the Morris water maze and fear condition paradigms when sponge delivered to hippocampi of 5XFAD and WT mice. miR-29a sponge expression significantly reduced hippocampal beta-amyloid deposition in 5XFAD mice and lowered astrocyte and microglia activation in both 5XFAD and WT mice. Using transcriptomic and proteomic sequencing, we identified Plxna1 and Wdfy1 as putative effectors at the transcript and protein level in WT and 5XFAD mice, respectively. These data indicate that miR-29a promotes AD-like neuropathology and negatively regulates cognition, making it and its target genes attractive therapeutic targets for the treatment of neurodegenerative disease. |
format | Online Article Text |
id | pubmed-10462195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-104621952023-08-29 Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice Mei, Zhen Liu, Jiaqi Schroeder, Jason P Weinshenker, David Duong, Duc M. Seyfried, Nicholas T. Li, Yujing Jin, Peng Wingo, Aliza P. Wingo, Thomas S. Res Sq Article microRNA-29a (miR-29a) increases with age in humans and mice, and, in the brain, it has a role in neuronal maturation and response to inflammation. We previously associated higher miR-29a levels in human brain with faster antemortem cognitive decline, suggesting that lowering miR-29a levels could ameliorate memory impairment in the 5xFAD AD mouse model. To test this hypothesis, we generated an adeno-associated virus (AAV) expressing GFP and a miR-29a “sponge” or empty vector. We found that the AAV expressing miR-29a sponge functionally reduced miR-29a levels, and improved measures of memory in the Morris water maze and fear condition paradigms when sponge delivered to hippocampi of 5XFAD and WT mice. miR-29a sponge expression significantly reduced hippocampal beta-amyloid deposition in 5XFAD mice and lowered astrocyte and microglia activation in both 5XFAD and WT mice. Using transcriptomic and proteomic sequencing, we identified Plxna1 and Wdfy1 as putative effectors at the transcript and protein level in WT and 5XFAD mice, respectively. These data indicate that miR-29a promotes AD-like neuropathology and negatively regulates cognition, making it and its target genes attractive therapeutic targets for the treatment of neurodegenerative disease. American Journal Experts 2023-08-16 /pmc/articles/PMC10462195/ /pubmed/37645711 http://dx.doi.org/10.21203/rs.3.rs-3235257/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Mei, Zhen Liu, Jiaqi Schroeder, Jason P Weinshenker, David Duong, Duc M. Seyfried, Nicholas T. Li, Yujing Jin, Peng Wingo, Aliza P. Wingo, Thomas S. Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice |
title | Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice |
title_full | Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice |
title_fullStr | Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice |
title_full_unstemmed | Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice |
title_short | Lowering hippocampal miR-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xFAD mice |
title_sort | lowering hippocampal mir-29a expression slows cognitive decline and reduces beta-amyloid deposition in 5xfad mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10462195/ https://www.ncbi.nlm.nih.gov/pubmed/37645711 http://dx.doi.org/10.21203/rs.3.rs-3235257/v1 |
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