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

TLDR

The study aimed to assess how acute and chronic voluntary exercise alter hippocampal gene expression. RNA from rats running for 3, 7, or 28 days was profiled with a brain‑enriched microarray and key genes were validated by RT‑PCR or RNase protection. Exercise induced robust up‑regulation of genes linked to synaptic trafficking, calcium‑dependent signaling, and transcription factors, with BDNF consistently increased, while glutamatergic genes rose and GABAergic genes fell, indicating BDNF’s central role and distinct temporal activation of CaM‑K and MAP‑K/ERK pathways.

Abstract

Abstract Studies were performed to determine the effects of acute and chronic voluntary periods of exercise on the expression of hippocampal genes. RNAs from rodents exposed to a running wheel for 3, 7 and 28 days were examined using a microarray with 1176 cDNAs expressed primarily in the brain. The expression of selected genes was quantified by Taqman RT‐PCR or RNase protection assay. The largest up‐regulation was observed in genes involved with synaptic trafficking (synapsin I, synaptotagmin and syntaxin); signal transduction pathways (Ca 2+ /calmodulin‐dependent protein kinase II, CaM‐KII; mitogen‐activated/extracellular signal‐regulated protein kinase, MAP‐K/ERK I and II; protein kinase C, PKC‐δ) or transcription regulators (cyclic AMP response element binding protein, CREB). Genes associated with the glutamatergic system were up‐regulated ( N ‐methyl‐ d ‐aspartate receptor, NMDAR‐2A and NMDAR‐2B and excitatory amino acid carrier 1, EAAC1), while genes related to the gamma‐aminobutyric acid (GABA) system were down‐regulated (GABA A receptor, glutamate decarboxylase GAD65). Brain‐derived neurotrophic factor (BDNF) was the only trophic factor whose gene was consistently up‐regulated at all timepoints. These results, together with the fact that most of the genes up‐regulated have a recognized interaction with BDNF, suggest a central role for BDNF on the effects of exercise on brain plasticity. The temporal profile of gene expression seems to delineate a mechanism by which specific molecular pathways are activated after exercise performance. For example, the CaM‐K signal system seems to be active during acute and chronic periods of exercise, while the MAP‐K/ERK system seems more important during long‐term exercise.