Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin

Int J Mol Sci. 2024 Jan 19;25(2):1213. doi: 10.3390/ijms25021213.

Abstract

The positive effects of physical exercise (EX) are well known to be mediated by cerebral BDNF (brain-derived neurotrophic factor), a neurotrophin involved in learning and memory, the expression of which could be induced by circulating irisin, a peptide derived from Fibronectin type III domain-containing protein 5 (FNDC5) produced by skeletal muscle contraction. While the influence of EX modalities on cerebral BDNF expression was characterized, their effect on muscle FNDC5/Irisin expression and circulating irisin levels remains to be explored. The present study involved Wistar rats divided into four experimental groups: sedentary (SED), low- (40% of maximal aerobic speed, MAS), intermediate- (50% of MAS) and high- (70% of MAS) intensities of treadmill EX (30 min/day, 7 days). Soleus (SOL) versus gastrocnemius (GAS) FNDC5 and hippocampal BDNF expressions were evaluated by Western blotting. Additionally, muscular FNDC5/Irisin localization and serum/hippocampal irisin levels were studied by immunofluorescence and ELISA, respectively. Our findings revealed that (1) serum irisin and hippocampal BDNF levels vary with EX intensity, showing a threshold intensity at 50% of MAS; (2) hippocampal BDNF levels positively correlate with serum irisin but not with hippocampal FNDC5/Irisin; and (3) GAS, in response to EX intensity, overexpresses FNDC5/Irisin in type II muscle fibers. Altogether, peripheral FNDC5/Irisin levels likely explain EX-dependent hippocampal BDNF expression.

Keywords: BDNF; FNDC5; hippocampus; irisin; muscle fibers; physical exercise intensity.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor* / genetics
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Fibronectins* / metabolism
  • Muscle, Skeletal / metabolism
  • Rats
  • Rats, Wistar
  • Transcription Factors / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Fibronectins
  • Transcription Factors
  • FNDC5 protein, rat