Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis

Abstract Aerobic exercise prevents age-dependent decline in cognition and hippocampal neurogenesis. The transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) mediates many of the exercise-induced benefits in skeletal muscle, including the release of fact...

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Autores principales:	Lars Karlsson, María Nazareth González-Alvarado, Reza Motalleb, Klas Blomgren, Mats Börjesson, Hans Georg Kuhn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/74f670ac4f37438ab1c911718eab4057
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spelling	oai:doaj.org-article:74f670ac4f37438ab1c911718eab40572021-12-02T15:08:45ZConstitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis10.1038/s41598-019-48795-w2045-2322https://doaj.org/article/74f670ac4f37438ab1c911718eab40572019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48795-whttps://doaj.org/toc/2045-2322Abstract Aerobic exercise prevents age-dependent decline in cognition and hippocampal neurogenesis. The transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) mediates many of the exercise-induced benefits in skeletal muscle, including the release of factors into the circulation with neurotrophic effects. We use a transgenic mouse model with muscle-specific overexpression of PGC-1α to study the contribution of chronic muscle activation on exercise-induced effects on hippocampal neurogenesis in aging. Young and old transgenic and wild type animals of both sexes displayed a robust age-related reduction in newborn BrdU+-cells, immature neurons (DCX+-cells) and new mature BrdU+/NeuN+-neurons in the dentate gyrus. No differences were detected between genotypes or sexes. Analysis of serum proteins showed a tendency towards increased levels of myokines and reduced levels of pro-inflammatory cytokines for transgenic animals, but only musclin was found to be significantly up-regulated in transgenic animals. We conclude that constitutive muscular overexpression of PGC-1α, despite potent systemic changes, is insufficient for mimicking exercise-induced effects on hippocampal neurogenesis in aging. Continued studies are required to investigate the complex molecular mechanisms by which circulating signals could mediate exercise-induced effects on the central nervous system in disease and aging, with the aim of discovering new therapeutic possibilities for patients.Lars KarlssonMaría Nazareth González-AlvaradoReza MotallebKlas BlomgrenMats BörjessonHans Georg KuhnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lars Karlsson María Nazareth González-Alvarado Reza Motalleb Klas Blomgren Mats Börjesson Hans Georg Kuhn Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
description	Abstract Aerobic exercise prevents age-dependent decline in cognition and hippocampal neurogenesis. The transcription factor peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) mediates many of the exercise-induced benefits in skeletal muscle, including the release of factors into the circulation with neurotrophic effects. We use a transgenic mouse model with muscle-specific overexpression of PGC-1α to study the contribution of chronic muscle activation on exercise-induced effects on hippocampal neurogenesis in aging. Young and old transgenic and wild type animals of both sexes displayed a robust age-related reduction in newborn BrdU+-cells, immature neurons (DCX+-cells) and new mature BrdU+/NeuN+-neurons in the dentate gyrus. No differences were detected between genotypes or sexes. Analysis of serum proteins showed a tendency towards increased levels of myokines and reduced levels of pro-inflammatory cytokines for transgenic animals, but only musclin was found to be significantly up-regulated in transgenic animals. We conclude that constitutive muscular overexpression of PGC-1α, despite potent systemic changes, is insufficient for mimicking exercise-induced effects on hippocampal neurogenesis in aging. Continued studies are required to investigate the complex molecular mechanisms by which circulating signals could mediate exercise-induced effects on the central nervous system in disease and aging, with the aim of discovering new therapeutic possibilities for patients.
format	article
author	Lars Karlsson María Nazareth González-Alvarado Reza Motalleb Klas Blomgren Mats Börjesson Hans Georg Kuhn
author_facet	Lars Karlsson María Nazareth González-Alvarado Reza Motalleb Klas Blomgren Mats Börjesson Hans Georg Kuhn
author_sort	Lars Karlsson
title	Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
title_short	Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
title_full	Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
title_fullStr	Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
title_full_unstemmed	Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
title_sort	constitutive pgc-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/74f670ac4f37438ab1c911718eab4057
work_keys_str_mv	AT larskarlsson constitutivepgc1aoverexpressioninskeletalmuscledoesnotprotectfromagedependentdeclineinneurogenesis AT marianazarethgonzalezalvarado constitutivepgc1aoverexpressioninskeletalmuscledoesnotprotectfromagedependentdeclineinneurogenesis AT rezamotalleb constitutivepgc1aoverexpressioninskeletalmuscledoesnotprotectfromagedependentdeclineinneurogenesis AT klasblomgren constitutivepgc1aoverexpressioninskeletalmuscledoesnotprotectfromagedependentdeclineinneurogenesis AT matsborjesson constitutivepgc1aoverexpressioninskeletalmuscledoesnotprotectfromagedependentdeclineinneurogenesis AT hansgeorgkuhn constitutivepgc1aoverexpressioninskeletalmuscledoesnotprotectfromagedependentdeclineinneurogenesis
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Constitutive PGC-1α overexpression in skeletal muscle does not protect from age-dependent decline in neurogenesis

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