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

By C. Wrann, James P. White, John Salogiannnis, Dina Laznik-Bogoslavski, Jun Wu, Di Ma, Jiandie D. Lin, Michael E. Greenberg, B. Spiegelman. Cell Metabolism, 2013

1,364 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/cbe7b8bbba26ae0785161d22ac3291f9faecb07d

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Citations in the corpus

Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020, background): “The PGC-1α-dependent myokine irisin, known for its browning effects (101), may also be involved in mediating effects of physical activity on the brain (98).”
Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate (2016, background): “For example, it has been reported that exercise induces Bdnf expression through the induction of hippocampal expression of Fndc5 (Wrann et al., 2013), a PGC-1a and ERRa -dependent myokine.”
Brain metabolism in health, aging, and neurodegeneration (2017, positive): “Another muscle-derived factor that has been suggested to mediate beneficial effects of exercise on neuroplasticity is irisin, which was reported to increase BDNF levels in the brain (Wrann et al, 2013).”
The Effects of Acute Exercise on Mood, Cognition, Neurophysiology, and Neurochemical Pathways: A Review (2016, background): “the release of BDNF in the hippocampus [170].”
Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults (2016, methodology): “The perfusion analyses are described in detail in Maass et al., 2015.”
Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis (2014, background): “It also induces a neuroprotective gene program in the hippocampi of treated animals (Wrann et al., 2013).”
Integrative biology of exercise. (2014, neutral): “…limited to IL-8, IL-15, decorin, follistatin-like 1, ﬁbroblast growth factor-21 (FGF21), irisin, chemokine CXC motif ligand-1 (CXCL-1) also known as KC (keratinocyte-derived chemokine), and mete-orin-like (Metrnl) (Bostro¨m et al., 2012; Rao et al., 2014; Pedersen et al., 2012; Wrann et al., 2013).”