title: Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.
abstract: 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.
authors.affiliation: Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Christiane D
authors.initials: CD
authors.lastname: Wrann
authors.forename: James P
authors.initials: JP
authors.lastname: White
authors.forename: John
authors.initials: J
authors.lastname: Salogiannnis
authors.forename: Dina
authors.initials: D
authors.lastname: Laznik-Bogoslavski
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Di
authors.initials: D
authors.lastname: Ma
authors.forename: Jiandie D
authors.initials: JD
authors.lastname: Lin
authors.forename: Michael E
authors.initials: ME
authors.lastname: Greenberg
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Spiegelman
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005822:Genetic Vectors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D011485:Protein Binding / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005353:Fibronectins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C571428:FNDC5 protein, mouse; C485290:Ppargc1a protein, mouse