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Exercise Modalities Improve Aversive Memory and Survival Rate in Aged Rats: Role of Hippocampal Epigenetic Modifications

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Abstract

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.

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Funding

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).

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  1. Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Louisiana Carolina Ferreira de Meireles, Fernando Galvão Jr, Laura Reck Cechinel, Carla Giovanna Basso & Ionara Rodrigues Siqueira

  2. Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Deena M. Walker & Eric J. Nestler

  3. Laboratório de Neuropsicofarmacologia, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, RS, CEP 90050-170, Brazil

    Ágnis Iohana de Souza Grefenhagen & Ionara Rodrigues Siqueira

  4. Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Gisele Andrade, Roberta Passos Palazzo & Ionara Rodrigues Siqueira

  5. Departamento de Fisioterapia, Universidade Federal de Santa Catarina, Araranguá, Santa Catarina, Brazil

    Gisele Agustini Lovatel

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  1. Louisiana Carolina Ferreira de Meireles
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Correspondence to Ionara Rodrigues Siqueira.

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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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de Meireles, L.C.F., Galvão, F., Walker, D.M. et al. Exercise Modalities Improve Aversive Memory and Survival Rate in Aged Rats: Role of Hippocampal Epigenetic Modifications. Mol Neurobiol 56, 8408–8419 (2019). https://doi.org/10.1007/s12035-019-01675-w

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