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

Journal article
Authors Lars O Karlsson
María Nazareth González-Alvarado
Reza Motalleb
K. Blomgren
Mats Börjesson
Hans-Georg Kuhn
Published in Scientific Reports
Volume 9
ISSN 2045-2322
Publication year 2019
Published at Institute of Neuroscience and Physiology
Language en
Links dx.doi.org/10.1038/s41598-019-48795...
Keywords adult hippocampal neurogenesis, dentate gyrus, mitochondrial biogenesis, neuromuscular-junction, physical-exercise, sex-differences, messenger-rna, estradiol, memory, vegf, Science & Technology - Other Topics
Subject categories Neurosciences

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-1 alpha) 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-1 alpha 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-1 alpha, 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.

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