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Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory
Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understoo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476098/ https://www.ncbi.nlm.nih.gov/pubmed/26095336 http://dx.doi.org/10.1038/srep11456 |
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author | Xu, Xu-Feng Li, Ting Wang, Dong-Dong Chen, Bing Wang, Yue Chen, Zhe-Yu |
author_facet | Xu, Xu-Feng Li, Ting Wang, Dong-Dong Chen, Bing Wang, Yue Chen, Zhe-Yu |
author_sort | Xu, Xu-Feng |
collection | PubMed |
description | Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understood. Here we show that integrin-linked kinase (ILK) levels are elevated upon EE stimuli in a BDNF-dependent manner. Using ILK-shRNA (siILK) lentivirus, we demonstrate that knockdown of ILK impairs EE-promoted hippocampal neurogenesis and memory by increasing glycogen synthase kinase-3β (GSK3β) activity. Finally, overexpressing ILK in the hippocampus could rescue the neurogenesis and memory deficits in BDNF(+/−) mice. These results indicate that ILK is indispensable for BDNF-mediated hippocampal neurogenesis and memory enhancement upon EE stimuli via regulating GSK3β activity. This is a new insight of the precise mechanism in EE-enhanced memory processes and ILK is a potentially important therapeutic target that merits further study. |
format | Online Article Text |
id | pubmed-4476098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-44760982015-06-24 Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory Xu, Xu-Feng Li, Ting Wang, Dong-Dong Chen, Bing Wang, Yue Chen, Zhe-Yu Sci Rep Article Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understood. Here we show that integrin-linked kinase (ILK) levels are elevated upon EE stimuli in a BDNF-dependent manner. Using ILK-shRNA (siILK) lentivirus, we demonstrate that knockdown of ILK impairs EE-promoted hippocampal neurogenesis and memory by increasing glycogen synthase kinase-3β (GSK3β) activity. Finally, overexpressing ILK in the hippocampus could rescue the neurogenesis and memory deficits in BDNF(+/−) mice. These results indicate that ILK is indispensable for BDNF-mediated hippocampal neurogenesis and memory enhancement upon EE stimuli via regulating GSK3β activity. This is a new insight of the precise mechanism in EE-enhanced memory processes and ILK is a potentially important therapeutic target that merits further study. Nature Publishing Group 2015-06-22 /pmc/articles/PMC4476098/ /pubmed/26095336 http://dx.doi.org/10.1038/srep11456 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Xu, Xu-Feng Li, Ting Wang, Dong-Dong Chen, Bing Wang, Yue Chen, Zhe-Yu Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory |
title | Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory |
title_full | Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory |
title_fullStr | Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory |
title_full_unstemmed | Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory |
title_short | Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory |
title_sort | integrin-linked kinase is essential for environmental enrichment enhanced hippocampal neurogenesis and memory |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476098/ https://www.ncbi.nlm.nih.gov/pubmed/26095336 http://dx.doi.org/10.1038/srep11456 |
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