Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
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
_version_ 1784578204501016576
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
work_keys_str_mv AT chenyuju follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT dengshinmeng follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT chenhuiwen follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT tsaochihui follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT chenweiting follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT chengsinjhong follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT huanghsiensung follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT tanbertrandchinming follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT matzukmartinm follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT flintjonathan follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus
AT huangguojen follistatinmediateslearningandsynapticplasticityviaregulationofasic4expressioninthehippocampus