Exercise Modalities Improve Aversive Memory and Survival Rate in Aged Rats: Role of Hippocampal Epigenetic Modifications
We aimed to investigate the effects of aging and different exercise modalities on aversive memory and epigenetic landscapes at brain-derived neurotrophic factor, cFos, and DNA methyltransferase 3 alpha (Bdnf, cFos, and Dnmt3a, respectively) gene promoters in hippocampus of rats. Specifically, active epigenetic histone markers (H3K9ac, H3K4me3, and H4K8ac) and a repressive mark (H3K9me2) were evaluated. Adult and aged male Wistar rats (2 and 22 months old) were subjected to aerobic, acrobatic, resistance, or combined exercise modalities for 20 min, 3 times a week, during 12 weeks. Aging per se altered histone modifications at the promoters of Bdnf, cFos, and Dnmt3a. All exercise modalities improved both survival rate and aversive memory performance in aged animals (n = 7–10). Exercise altered hippocampal epigenetic marks in an age- and modality-dependent manner (n = 4–5). Aerobic and resistance modalities attenuated age-induced effects on hippocampal Bdnf promoter H3K4me3. Besides, exercise modalities which improved memory performance in aged rats were able to modify H3K9ac or H3K4me3 at the cFos promoter, which could increase gene transcription. Our results highlight biological mechanisms which support the efficacy of all tested exercise modalities attenuating memory deficits induced by aging.
KeywordsExercise Rats Inhibitory avoidance Aging Histone methylation Histone acetylation Bdnf cFos Dnmt3a
This work was supported, in part, by grant PDSE - 88881.135752/2016-01 from Comissão de Aperfeiçoamento de Pessoal (CAPES) from Brazil and P50MH096890 from the US National Institute of Mental Health (E.J. Nestler). CNPq fellowships (Dr. I.R. Siqueira; L.C.F. Meireles, K. Bertoldi and L. R. Cechinel) CAPES fellowship (F.J. Galvão).
Compliance with Ethical Standards
The NIH “Guide for the Care and Use of Laboratory Animals” (NIH publication no. 80–23, revised 1996) was followed in all experiments. The Local Ethics Committee approved all handling and experimental conditions (no. 29818).
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