Transforming growth factor-beta activated during exercise in brain depresses spontaneous motor activity of animals. Relevance To central fatigue

Brain Res. 1999 Nov 6;846(2):145-53. doi: 10.1016/s0006-8993(99)01966-6.


Intracerebroventricular administration into sedentary mice of the high molecular mass fraction of cerebrospinal fluid (CSF) from exercise-exhausted rats produced a decrease in spontaneous motor activity [K. Inoue, H. Yamazaki, Y. Manabe, C. Fukuda, T. Fushiki, Release of a substance that suppresses spontaneous motor activity in the brain by physical exercise, Physiol. Behav. 64 (1998) 185-190]. CSF from sedentary rats had no such effect. This suggests the presence of a substance regulating the urge for motion as a response to fatigue. A bioassay system using hydra, a freshwater coelenterate, showed an activity indistinguishable from transforming growth factor-beta (TGF-beta) in the CSF from exercise-fatigued rats, while not in that from sedentary rats. The increase in the concentration of active TGF-beta in the CSF from exercise-fatigued rat was also ascertained by another bioassay system using mink lung epithelial cells (Mv1Lu). Injection of TGF-beta into the brains of sedentary mice elicited a similar decrease in spontaneous motor activity in a dose-dependent manner. Increasing the exercise load on rats raised both the levels of active TGF-beta and the activity of depression on spontaneous motor activity of mice in the CSF of rats. Taken together, these results suggest that exercise increases active TGF-beta in the brain and it creates the feeling of fatigue and thus suppresses spontaneous motor activity.

MeSH terms

  • Animals
  • Antibodies
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Biological Assay
  • Brain Chemistry / physiology
  • Enkephalin, Methionine / pharmacology
  • Fatigue / physiopathology*
  • Fibroblast Growth Factor 2 / pharmacology
  • Hydra
  • Immunoglobulin G / pharmacology
  • Male
  • Mice
  • Microinjections
  • Motor Activity / drug effects
  • Motor Activity / physiology*
  • Physical Exertion / drug effects
  • Physical Exertion / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Thyrotropin-Releasing Hormone / pharmacology
  • Transforming Growth Factor beta / cerebrospinal fluid*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / pharmacology


  • Antibodies
  • Immunoglobulin G
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2
  • Enkephalin, Methionine
  • Thyrotropin-Releasing Hormone