Finding a protein linking exercise to brain health

Yet another candidate for a life enhancing drug? ...perhaps a protein that mimics the effect of the protein FNDC5, which is produced by muscular exertion and in turn boosts the level of a brain-health protein, BDNF (brain-derived neurotrophic protein) in the dentate gyrus of the hippocampus. Here is the summary and abstract from Wrann et al. with some technical details:

Highlights

Exercise induces FNDC5 in the hippocampus.

PGC-1α regulates neuronal Fndc5 gene expression in vitro and in vivo.

FNDC5 positively regulates the expression of the important neurotrophin BDNF.

Peripheral delivery of FNDC5 via adenoviral vectors induces Bdnf in the hippocampus.

Summary

Exercise can improve cognitive function and has been linked to the increased expression of brain-derived neurotrophic factor (BDNF). However, the underlying molecular mechanisms driving the elevation of this neurotrophin remain unknown. Here we show that FNDC5, a previously identified muscle protein that is induced in exercise and is cleaved and secreted as irisin, is also elevated by endurance exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated by PGC-1α, and Pgc1a−/− mice show reduced Fndc5 expression in the brain. Forced expression of FNDC5 in primary cortical neurons increases Bdnf expression, whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated blood irisin, induces expression of Bdnf and other neuroprotective genes in the hippocampus. Taken together, our findings link endurance exercise and the important metabolic mediators, PGC-1α and FNDC5, with BDNF expression in the brain.