EXERCISE-INDUCED REGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR (BDNF) TRANSCRIPTS IN THE RAT HIPPOCAMPUS

Previous results from our laboratory indicate that two nights of volun tary wheel running upregulates brain-derived neurotrophic factor (BDNF ) mRNA expression in the hippocampus. In order to investigate the time -course of the BDNF response and to examine how physical activity pref erentially activates particular transcriptional pathways, the effects of 6 and 12 h of voluntary wheel running on BDNF and exons I-IV mRNA e xpression were investigated in rats. Hippocampal full-length BDNF mRNA expression was rapidly influenced by physical activity, showing signi ficant increases in expression levels as soon as 6 h of voluntary whee l running. Moreover, there was a strong positive correlation between d istance run and BDNF mRNA expression. Exon I mRNA expression was signi ficantly upregulated after 6 h of running and was maintained or enhanc ed by 12 h of voluntary running. Exon II had a slower time-course and was significantly upregulated after 12 h, selectively in the CA1 hippo campal region. Exon III and Exon IV showed no significant increase in expression level after 6 or 12 h of running in the paradigm studied. I t is significant that the rapid neurotrophin response is demonstrated for a physiologically relevant stimulus, as opposed to the extreme con ditions of seizure paradigms. Furthermore, exercise-induced upregulati on of BDNF may help increase the brain's resistance to damage and neur odegeneration that occurs with aging. (C) 1998 Elsevier Science B.V. A ll rights reserved.