Constitutive PGC-1α Overexpression in Skeletal Muscle Does Not Contribute to Exercise-Induced Neurogenesis

Abstract

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.

Pristane induced lupus mice as a model for neuropsychiatric lupus (NPSLE)

“…Differences in normally distributed data were detected by repeated measures analysis of variance (ANOVA) (with time as within factor and group [PBS, pristane] as between factor) followed by Tukey's post hoc test for multiple comparison. For non-parametric data, the Scheirer–Ray–Hare extension of the Kruskal–Wallis test [ 83 ] was used as a non-parametric equivalent of the two-way ANOVA. p < 0.05 was considered a statistically significant difference in all sampled groups.…”

High Intensity Acute Aerobic Exercise Elicits Alterations in Circulating and Skeletal Muscle Tissue Expression of Neuroprotective Exerkines

“…The lack of change in CTSB transcript may be explained by transcription factors that regulate CTSB gene expression. Activation of both AMPK and peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1␣) led to significant increases in CTSB transcript in skeletal muscle cells [24,61]. Therefore, acute AE may facilitate skeletal muscle CTSB expression via AMPK-PGC1␣ signaling.…”