Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wrann, CD; White, JP; Salogiannnis, J; Laznik-Bogoslavski, D; Wu, J; Ma, D; Lin, JD; Greenberg, ME; Spiegelman, BM

Published Date

  • November 2013

Published In

Volume / Issue

  • 18 / 5

Start / End Page

  • 649 - 659

PubMed ID

  • 24120943

Pubmed Central ID

  • 24120943

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2013.09.008

Language

  • eng