Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis.
Aging
Hippocampal neurogenesis
Immunohistochemistry
PGC-1α
Transgenic mice
Voluntary running
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
25
05
2020
accepted:
27
10
2020
pubmed:
18
11
2020
medline:
28
10
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
Physical exercise can improve age-dependent decline in cognition, which in rodent is partly mediated by restoration of an age-dependent decline in neurogenesis. Exercise-inducible myokines in the circulation present a link in muscle-brain crosstalk. The transcription factor PGC-1α regulates the release of such myokines with neurotrophic properties into the circulation. We study how chronic muscular overexpression of PGC-1α could contribute to exercise-induced effects on hippocampal neurogenesis and if this effect could be enhanced in a running wheel paradigm. We used 3- and 11-month-old transgenic mice with overexpression of PGC-1α under the control of muscle creatinine kinase promoter (MCK-PGC-1α), which have a constitutively developed endurance muscle phenotype. Wild-type and MCK-PGC-1α mice were single housed with free access to running wheels. Four weeks of running in female animals increased the levels of newborn cells, immature neurons, and, for young animals, new mature neurons, compared to sedentary controls. However, no difference in these parameters was observed between wild-type and transgenic mice under sedentary or running conditions. Multiplex analysis of serum cytokines, chemokines, and myokines suggested several differences in serum protein concentrations between genotypes with musclin found to be significantly upregulated 4-fold in male MCK-PGC-1α animals. We conclude that constitutive muscular overexpression of PGC-1α, despite systemic changes and difference in serum composition, does not translate into exercise-induced effects on hippocampal neurogenesis, independent of the age of the animal. This suggests that chronic activation of PGC-1α in skeletal muscle is by itself not sufficient to mimic exercise-induced effects or to prevent decline of neurogenesis in aging.
Identifiants
pubmed: 33200398
doi: 10.1007/s12035-020-02189-6
pii: 10.1007/s12035-020-02189-6
pmc: PMC7932943
doi:
Substances chimiques
Cytokines
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1465-1481Subventions
Organisme : Vetenskapsrådet
ID : 721-2014-2468/521-2014-3224
Organisme : Barncancerfonden
ID : MT2017-0013
Organisme : Sahlgrenska Universitetssjukhuset
ID : ALFGBG726541
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