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Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus
The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing informati...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488609/ https://www.ncbi.nlm.nih.gov/pubmed/34544873 http://dx.doi.org/10.1073/pnas.2109040118 |
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author | Chen, Yu-Ju Deng, Shin-Meng Chen, Hui-Wen Tsao, Chi-Hui Chen, Wei-Ting Cheng, Sin-Jhong Huang, Hsien-Sung Tan, Bertrand Chin-Ming Matzuk, Martin M. Flint, Jonathan Huang, Guo-Jen |
author_facet | Chen, Yu-Ju Deng, Shin-Meng Chen, Hui-Wen Tsao, Chi-Hui Chen, Wei-Ting Cheng, Sin-Jhong Huang, Hsien-Sung Tan, Bertrand Chin-Ming Matzuk, Martin M. Flint, Jonathan Huang, Guo-Jen |
author_sort | Chen, Yu-Ju |
collection | PubMed |
description | The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis. We confirmed that brain-specific Fst knockout (KO) mice exhibited decreased hippocampal neurogenesis and demonstrated that FST is critical for learning. Fst KO mice exhibit deficits in spatial learning, working memory, and long-term potentiation (LTP). In contrast, hippocampal overexpression of Fst in KO mice reversed these impairments. By utilizing RNA sequencing and chromatin immunoprecipitation, we identified Asic4 as a target gene regulated by FST and show that Asic4 plays a critical role in learning deficits caused by Fst deletion. Long-term overexpression of hippocampal Fst in C57BL/6 wild-type mice alleviates age-related decline in cognition, neurogenesis, and LTP. Collectively, our study reveals the functions for FST in adult neurogenesis and learning behaviors. |
format | Online Article Text |
id | pubmed-8488609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-84886092021-10-25 Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus Chen, Yu-Ju Deng, Shin-Meng Chen, Hui-Wen Tsao, Chi-Hui Chen, Wei-Ting Cheng, Sin-Jhong Huang, Hsien-Sung Tan, Bertrand Chin-Ming Matzuk, Martin M. Flint, Jonathan Huang, Guo-Jen Proc Natl Acad Sci U S A Biological Sciences The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis. We confirmed that brain-specific Fst knockout (KO) mice exhibited decreased hippocampal neurogenesis and demonstrated that FST is critical for learning. Fst KO mice exhibit deficits in spatial learning, working memory, and long-term potentiation (LTP). In contrast, hippocampal overexpression of Fst in KO mice reversed these impairments. By utilizing RNA sequencing and chromatin immunoprecipitation, we identified Asic4 as a target gene regulated by FST and show that Asic4 plays a critical role in learning deficits caused by Fst deletion. Long-term overexpression of hippocampal Fst in C57BL/6 wild-type mice alleviates age-related decline in cognition, neurogenesis, and LTP. Collectively, our study reveals the functions for FST in adult neurogenesis and learning behaviors. National Academy of Sciences 2021-09-28 2021-09-20 /pmc/articles/PMC8488609/ /pubmed/34544873 http://dx.doi.org/10.1073/pnas.2109040118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Chen, Yu-Ju Deng, Shin-Meng Chen, Hui-Wen Tsao, Chi-Hui Chen, Wei-Ting Cheng, Sin-Jhong Huang, Hsien-Sung Tan, Bertrand Chin-Ming Matzuk, Martin M. Flint, Jonathan Huang, Guo-Jen Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus |
title | Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus |
title_full | Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus |
title_fullStr | Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus |
title_full_unstemmed | Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus |
title_short | Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus |
title_sort | follistatin mediates learning and synaptic plasticity via regulation of asic4 expression in the hippocampus |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488609/ https://www.ncbi.nlm.nih.gov/pubmed/34544873 http://dx.doi.org/10.1073/pnas.2109040118 |
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