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Astroglia-derived BDNF and MSK-1 mediate experience- and diet-dependent synaptic plasticity
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Lalo, Ulyana, Bogdanov, Alexander, Moss, Guy W. and Pankratov, Yuriy (2020) Astroglia-derived BDNF and MSK-1 mediate experience- and diet-dependent synaptic plasticity. Brain sciences, 10 (7). 462. doi:10.3390/brainsci10070462 ISSN 2076-3425.
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Official URL: https://doi.org/10.3390/brainsci10070462
Abstract
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 Ca2+ 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.
Item Type: | Journal Article | ||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | ||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||
Library of Congress Subject Headings (LCSH): | Neuroplasticity -- Research | ||||||||||||
Journal or Publication Title: | Brain sciences | ||||||||||||
Publisher: | MDPI | ||||||||||||
ISSN: | 2076-3425 | ||||||||||||
Official Date: | 18 July 2020 | ||||||||||||
Dates: |
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Volume: | 10 | ||||||||||||
Number: | 7 | ||||||||||||
Article Number: | 462 | ||||||||||||
DOI: | 10.3390/brainsci10070462 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | Published | ||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
Copyright Holders: | © 2020 by the authors | ||||||||||||
Date of first compliant deposit: | 4 September 2020 | ||||||||||||
Date of first compliant Open Access: | 7 September 2020 | ||||||||||||
RIOXX Funder/Project Grant: |
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