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

Intracerebroventricular administration into sedentary mice of the high mole cular mass fraction of cerebrospinal fluid (CSF) from exercise-exhausted ra ts 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. Beha v. 64 (1998) 185-190]. CSF from sedentary rats had no such effect. This sug gests the presence of a substance regulating the urge for motion as a respo nse to fatigue. A bioassay system using hydra, a freshwater coelenterate, s howed an activity indistinguishable from transforming growth factor-beta (T GF-beta) in the CSF from exercise-fatigued rats, while not in that from sed entary rats. The increase in the concentration of active TGF-beta in the CS F from exercise-fatigued rat was also ascertained by another bioassay syste m using mink lung epithelial cells (Mv1Lu). Injection of TGF-beta into the brains of sedentary mice elicited a similar decrease in spontaneous motor a ctivity in a dose-dependent manner. Increasing the exercise load on rats ra ised both the levels of active TGF-beta and the activity of depression on s pontaneous motor activity of mice in the CSF of rats. Taken together, these results suggest that exercise increases active TGF-beta in the brain and i t creates the feeling of fatigue and thus suppresses spontaneous motor acti vity. (C) 1999 Elsevier Science B.V. All rights reserved.