Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus
H. Shen et al., Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus, NEUROSCIENC, 107(2), 2001, pp. 219-229
To elucidate molecular mechanisms involved in physical activity-induced ben
eficial effects on brain function. we studied in rats the influence of volu
ntary running on the activation in the hippocampus of cyclic AMP response e
lement-binding protein (CREB) and mitogen-activated protein kinase (MAPK)/e
xtracellular signal-regulated protein kinase (ERK). These are signaling mol
ecules that play critical roles in synaptic plasticity, including learning
and memory, Exercise resulted in an increase in the level of the activated
transcription factor. CREB phosphorylated at Ser-133. The amount of the act
ivated transcription Factor about doubled already after I night of running
and remained elevated for at least a week, although control levels were res
tored after I month of exercise. In addition, binding activity in nuclear e
xtracts to cyclic AMP response element (CRE) motif containing oligonucleoti
des increased significantly in the hippocampus after 3 nights of exercise.
although the total amount of the immunochemically identified CREB remained
unaltered. Electrophoretic mobility supershift assays indicated that the in
creased binding was due to the recruitment of members of this transcription
Factor family. in addition to the CREB proper. Voluntary running also resu
lted in an increase in the level of phosphorylated MAPK (both p42 and p44).
The time-courses of the increases in the level of the phosphorylated prote
in kinase and the activated transcription factor were different. In compari
son with the activated CREB, the increase in the phosphorylated MAPK was de
layed, but lasted longer, being detectable even after I month of exercise.
These observations are consistent with the view that the relatively long-la
sting activation of these signaling molecules participates in the regulatio
n of genes. such as the neurotrophin genes, and contributes to the benefici
al effects of physical exercise on brain function. (C), 2001 Published by E
lsevier Science Ltd on behalf of IBRO.