Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray.

Eur J Neurosci. 2002 Sep;16(6):1107-16. Molteni R, Ying Z, Gómez-Pinilla F. In this study the authors determined the effects of acute and chronic voluntary periods of exercise on the expression of genes in the hippocampus. The authors used a predesigned microarray with 1176 cDNAs primarily expressed in the brain. The animals were allowed to run voluntarily for a period of 3, 7 and 28 days. Sedentary animals were used as control. Genes associated with glutamatergic system such as NMDAR-2A, NMDAR-2B and excitatory amino acid carrier-1 was upregulated, where as GABAA receptor and GAD 65 were down-regulated. BDNF genes were consistently up-regulated across all different exercise groups. The authors hypothesized a potential mechanism by which exercise modulates neuronal plasticity in the hippocampus. It was suggested elevated BDNF expression under active conditions could affect both the pre and post synaptic terminals. TrKB receptor, the primary mediator of BDNF was also up-regulated in active animals. TrKB signaling affected the up-regulation of several downstream genes such as MAP-KI, MAP-KII, PKC gamma and CaM-KII. The authors also suggest that exercise could affect the pre synaptic genes such as synapsin, synaptotagmin and syntaxin to modulate the release of neurotransmitters such as glutamate. In the post synaptic terminal, the effects of exercise could be mediated by calcium influx through the NMDA receptor. The expression of calcium2+/calmodulin dependent protein kinase II was also up-regulated in exercise, which could activate the MAP-K cascade. Activated MAP-K could act on a nuclear target, transcription factor CREB, the expression of which is also up-regulated in exercise. -Madhan