A study of how exercise impacts neuronal and cognitive function via a BDNF-mediated mechanism.

摘要

The pervasive effect of exercise on cognitive function has been well described. Exercise improves learning and memory, ameliorates cognitive deficits associated with depression, facilitates functional recovery from neurological dysfunction, and even counteracts the mental decline associated with aging. Yet, the mechanisms sub-serving the ability of exercise to enhance neuronal and cognitive function have remained elusive. This study was designed to identify molecular mechanisms by which exercise affects learning and memory, specifically by studying synaptic-plasticity in the hippocampus, a brain area whose function, learning and memory, depends on this capability. We have focused on the central role that brain-derived neurotrophic factor (BDNF) may play in mediating the effects of exercise on cognition and synaptic-plasticity and have evaluated the contribution of different pathways to the exercise-induced increases in the mRNA levels of BDNF, TrkB, CREB, and synapsin I. Identifying short exercise duration capable of enhancing cognitive function on the Morris water maze (MWM) enabled this study to examine whether a BDNF-mediated mechanism sub-serves the capacity of exercise to improve hippocampal-dependent learning. A novel microbead injection technique was used to selectively target molecular systems in the hippocampus by using specific blockers to BDNF, the N-methyl-D-aspartate receptor (NMDA-R), calcium/calmodulin protein kinase II (CAMKII), the mitogen-activated protein kinase (MAP-K) cascade, and the uncoupling protein (UCP) 2. Inhibiting BDNF action during the exercise period blocked the benefit of exercise on cognitive function, such that the learning and recall abilities of exercising animals receiving the BDNF blocker were reduced to sedentary control levels. Inhibiting BDNF action also blocked the effect of exercise on downstream systems regulated by BDNF and important for synaptic plasticity, CREB and synapsin I. The findings of this study show that although BDNF mediates exercise-induced hippocampal plasticity, additional molecules, i.e., the NMDA receptor, CAMKII, the MAP-K cascade, and UCP2 modulate its effects. The well-described association of these molecules to BDNF action enables the results of this study to illustrate a basic mechanism through which exercise may promote learning and memory and synaptic-plasticity in the adult brain.