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

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2019 Jun 29

PMID 31250382

Citations 15

Authors

Louisiana Carolina Ferreira de Meireles

Fernando Galvao Jr

Deena M Walker

Laura Reck Cechinel

Agnis Iohana de Souza Grefenhagen

Gisele Andrade

Roberta Passos Palazzo

Gisele Agustini Lovatel

Carla Giovanna Basso

Eric J Nestler

Ionara Rodrigues Siqueira

Affiliations

Soon will be listed here.

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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References

Woo N, Teng H, Siao C, Chiaruttini C, Pang P, Milner T . Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat Neurosci. 2005; 8(8):1069-77. DOI: 10.1038/nn1510. View

Novaes Gomes F, Fernandes J, Campos D, Cassilhas R, Viana G, DAlmeida V . The beneficial effects of strength exercise on hippocampal cell proliferation and apoptotic signaling is impaired by anabolic androgenic steroids. Psychoneuroendocrinology. 2014; 50:106-17. DOI: 10.1016/j.psyneuen.2014.08.009. View

Cechinel L, Basso C, Bertoldi K, Schallenberger B, de Meireles L, Siqueira I . Treadmill exercise induces age and protocol-dependent epigenetic changes in prefrontal cortex of Wistar rats. Behav Brain Res. 2016; 313:82-87. DOI: 10.1016/j.bbr.2016.07.016. View

Nelson M, Rejeski W, Blair S, Duncan P, Judge J, King A . Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Circulation. 2007; 116(9):1094-105. DOI: 10.1161/CIRCULATIONAHA.107.185650. View

Graff J, Mansuy I . Epigenetic dysregulation in cognitive disorders. Eur J Neurosci. 2009; 30(1):1-8. DOI: 10.1111/j.1460-9568.2009.06787.x. View

Berchtold N, Castello N, Cotman C . Exercise and time-dependent benefits to learning and memory. Neuroscience. 2010; 167(3):588-97. PMC: 2857396. DOI: 10.1016/j.neuroscience.2010.02.050. View

Elsner V, Lovatel G, Moyses F, Bertoldi K, Spindler C, Cechinel L . Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study. Exp Gerontol. 2012; 48(2):136-9. PMC: 4405233. DOI: 10.1016/j.exger.2012.11.011. View

Ono T, Uehara Y, Kurishita A, Tawa R, Sakurai H . Biological significance of DNA methylation in the ageing process. Age Ageing. 1993; 22(1):S34-43. DOI: 10.1093/ageing/22.suppl_1.s34. View

Simpson R, Lowder T, Spielmann G, Bigley A, Lavoy E, Kunz H . Exercise and the aging immune system. Ageing Res Rev. 2012; 11(3):404-20. DOI: 10.1016/j.arr.2012.03.003. View

10.

Garcia P, Real C, Ferreira A, Alouche S, Britto L, Pires R . Different protocols of physical exercise produce different effects on synaptic and structural proteins in motor areas of the rat brain. Brain Res. 2012; 1456:36-48. DOI: 10.1016/j.brainres.2012.03.059. View

11.

Bayraktar G, Kreutz M . Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity and Gene Expression?. Neuroscientist. 2017; 24(2):171-185. PMC: 5846851. DOI: 10.1177/1073858417707457. View

12.

Silhol M, Arancibia S, Maurice T, Tapia-Arancibia L . Spatial memory training modifies the expression of brain-derived neurotrophic factor tyrosine kinase receptors in young and aged rats. Neuroscience. 2007; 146(3):962-73. DOI: 10.1016/j.neuroscience.2007.02.013. View

13.

Arida R, Scorza F, dos Santos N, Peres C, Cavalheiro E . Effect of physical exercise on seizure occurrence in a model of temporal lobe epilepsy in rats. Epilepsy Res. 1999; 37(1):45-52. DOI: 10.1016/s0920-1211(99)00032-7. View

14.

Dawson M, Kouzarides T . Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150(1):12-27. DOI: 10.1016/j.cell.2012.06.013. View

15.

Abel J, Rissman E . Running-induced epigenetic and gene expression changes in the adolescent brain. Int J Dev Neurosci. 2012; 31(6):382-90. PMC: 3686974. DOI: 10.1016/j.ijdevneu.2012.11.002. View

16.

da Silva I, de Araujo C, Dorneles G, Peres A, Bard A, Reinaldo G . Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study. Respir Physiol Neurobiol. 2017; 242:89-95. DOI: 10.1016/j.resp.2017.04.004. View

17.

Wang Z, Zang C, Rosenfeld J, Schones D, Barski A, Cuddapah S . Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008; 40(7):897-903. PMC: 2769248. DOI: 10.1038/ng.154. View

18.

Teng H, Teng K, Lee R, Wright S, Tevar S, Almeida R . ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci. 2005; 25(22):5455-63. PMC: 6724992. DOI: 10.1523/JNEUROSCI.5123-04.2005. View

19.

Li Z, Peng X, Xiang W, Han J, Li K . The effect of resistance training on cognitive function in the older adults: a systematic review of randomized clinical trials. Aging Clin Exp Res. 2018; 30(11):1259-1273. DOI: 10.1007/s40520-018-0998-6. View

20.

Akbarian S, Beeri M, Haroutunian V . Epigenetic determinants of healthy and diseased brain aging and cognition. JAMA Neurol. 2013; 70(6):711-8. PMC: 3932340. DOI: 10.1001/jamaneurol.2013.1459. View