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

Publication ,  Journal Article
Wrann, CD; White, JP; Salogiannnis, J; Laznik-Bogoslavski, D; Wu, J; Ma, D; Lin, JD; Greenberg, ME; Spiegelman, BM
Published in: Cell Metab
November 5, 2013

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.

Duke Scholars

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

November 5, 2013

Volume

18

Issue

5

Start / End Page

649 / 659

Location

United States

Related Subject Headings

  • Transcription Factors
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Estrogen
  • Protein Binding
  • Physical Conditioning, Animal
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Neurons
  • Mice, Inbred C57BL
  • Mice
 

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Wrann, C. D., White, J. P., Salogiannnis, J., Laznik-Bogoslavski, D., Wu, J., Ma, D., … Spiegelman, B. M. (2013). Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab, 18(5), 649–659. https://doi.org/10.1016/j.cmet.2013.09.008
Wrann, Christiane D., James P. White, John Salogiannnis, Dina Laznik-Bogoslavski, Jun Wu, Di Ma, Jiandie D. Lin, Michael E. Greenberg, and Bruce M. Spiegelman. “Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.Cell Metab 18, no. 5 (November 5, 2013): 649–59. https://doi.org/10.1016/j.cmet.2013.09.008.
Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013 Nov 5;18(5):649–59.
Wrann, Christiane D., et al. “Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway.Cell Metab, vol. 18, no. 5, Nov. 2013, pp. 649–59. Pubmed, doi:10.1016/j.cmet.2013.09.008.
Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME, Spiegelman BM. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013 Nov 5;18(5):649–659.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

November 5, 2013

Volume

18

Issue

5

Start / End Page

649 / 659

Location

United States

Related Subject Headings

  • Transcription Factors
  • Signal Transduction
  • Recombinant Proteins
  • Receptors, Estrogen
  • Protein Binding
  • Physical Conditioning, Animal
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Neurons
  • Mice, Inbred C57BL
  • Mice