Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray.
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 (Ca2+/calmodulin-dependent protein kinase II, CaM-KII; mitogen-activated/extracellular signal-regulated protein kinase, MAP-K/ERK I and II; protein kinase C, PKC-delta) 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 (GABAA 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.
Molteni
Raffaella
R
Division of Neurosurgery, UCLA Brain Injury Research Center and Department of Physiological Science, UCLA, 621 Charles E. Young Drive Los Angeles California 90095, USA.
Ying
Zhe
Z
Gómez-Pinilla
Fernando
F
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010805:Physical Conditioning, Animal; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000235:genetics; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
D019208:Brain-Derived Neurotrophic Factor; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins