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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

adult hippocampal neurogenesis

dentate gyrus

mitochondrial biogenesis

neuromuscular-junction

physical-exercise

sex-differences

messenger-rna

estradiol

memory

vegf

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