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Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity †
Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astrog...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407492/ https://www.ncbi.nlm.nih.gov/pubmed/32708382 http://dx.doi.org/10.3390/brainsci10070462 |
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author | Lalo, Ulyana Bogdanov, Alexander Moss, Guy W. Pankratov, Yuriy |
author_facet | Lalo, Ulyana Bogdanov, Alexander Moss, Guy W. Pankratov, Yuriy |
author_sort | Lalo, Ulyana |
collection | PubMed |
description | Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release BDNF via a calcium-dependent mechanism. To elucidate a role for astroglia-derived BDNF in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the BDNF/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused BDNF-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca(2+) signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of BDNF is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain. |
format | Online Article Text |
id | pubmed-7407492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74074922020-08-25 Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † Lalo, Ulyana Bogdanov, Alexander Moss, Guy W. Pankratov, Yuriy Brain Sci Article Experience- and diet-dependent regulation of synaptic plasticity can underlie beneficial effects of active lifestyle on the aging brain. Our previous results demonstrate a key role for brain-derived neurotrophic factor (BDNF) and MSK1 kinase in experience-related homeostatic synaptic scaling. Astroglia has been recently shown to release BDNF via a calcium-dependent mechanism. To elucidate a role for astroglia-derived BDNF in homeostatic synaptic plasticity in the aging brain, we explored the experience- and diet-related alterations of synaptic transmission and plasticity in transgenic mice with impairment of the BDNF/MSK1 pathway (MSK1 kinase dead knock-in mice, MSK1 KD) and impairment of glial exocytosis (dnSNARE mice). We found that prolonged tonic activation of astrocytes caused BDNF-dependent increase in the efficacy of excitatory synapses accompanied by enlargement of synaptic boutons. We also observed that exposure to environmental enrichment (EE) and caloric restriction (CR) enhanced the Ca(2+) signalling in cortical astrocytes and strongly up-regulated the excitatory and down-regulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on astroglial and synaptic signalling. The EE- and CR-induced up-scaling of excitatory synaptic transmission in neocortex was accompanied by the enhancement of long-term synaptic potentiation. Importantly, effects of EE and CR on synaptic transmission and plasticity was significantly reduced in the MSK1 KD and dnSNARE mice. Combined, our results suggest that astroglial release of BDNF is important for the homeostatic regulation of cortical synapses and beneficial effects of EE and CR on synaptic transmission and plasticity in aging brain. MDPI 2020-07-18 /pmc/articles/PMC7407492/ /pubmed/32708382 http://dx.doi.org/10.3390/brainsci10070462 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lalo, Ulyana Bogdanov, Alexander Moss, Guy W. Pankratov, Yuriy Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † |
title | Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † |
title_full | Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † |
title_fullStr | Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † |
title_full_unstemmed | Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † |
title_short | Astroglia-Derived BDNF and MSK-1 Mediate Experience- and Diet-Dependent Synaptic Plasticity † |
title_sort | astroglia-derived bdnf and msk-1 mediate experience- and diet-dependent synaptic plasticity † |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407492/ https://www.ncbi.nlm.nih.gov/pubmed/32708382 http://dx.doi.org/10.3390/brainsci10070462 |
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