Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: A preliminary study

Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, Rua Sarmento Leite, 500, 90050-170, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Experimental gerontology (Impact Factor: 3.49). 11/2012; 48(2). DOI: 10.1016/j.exger.2012.11.011
Source: PubMed


Regular exercise improves learning and memory, including during aging process. Interestingly, the imbalance of epigenetic mechanisms has been linked to age-related cognitive deficits. However, studies about epigenetic alterations after exercise during the aging process are rare. In this preliminary study we investigated the effect of aging and exercise on DNA methyltransferases (DNMT1 and DNMT3b) and H3-K9 methylation levels in hippocampus from 3 and 20-months aged Wistar rats. The animals were submitted to two exercise protocols: single session or chronic treadmill protocol. DNMT1 and H3-K9 methylation levels were decreased in hippocampus from aged rats. The single exercise session decreased both DNMT3b and DNMT1 levels in young adult rats, without any effect in the aged group. Both exercise protocols reduced H3-K9 methylation levels in young adult rats, while the single session reversed the changes on H3-K9 methylation levels induced by aging. Together, these results suggest that an imbalance on DNMTs and H3-K9 methylation levels might be linked to the brain aging process and that the outcome to exercise seems to vary through lifespan.

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    • "Recently, Elsner et al. [17] demonstrated using Wistar rats that exercise performed on a treadmill affect acetylation levels in the hippocampus through modulation of the activities of Histone Acetyl Transferases (HAT) and Histone Deacetylases (HDAC). "
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    ABSTRACT: Epigenetics has recently been linked to molecular adaptive responses evoked by physical exercise and stress. Herein we evaluated the effects of physical exercise on global DNA methylation and expression of the Dnmt1 gene in the rat brain and also verified its potential to modulate responses evoked by repeated restraint stress (RRS). Wistar rats were classified into the following experimental groups: 1) physically active (EX): animals submitted to swimming during postnatal days 53-78 (PND); 2) Stress (ST): animals submitted to RRS during 75-79PND; 3) Exercise-stress (EX-ST): animals submitted to swimming during 53-78PND and to RRS during 75-79PND, and 4) Control (CTL): animals that were not submitted to intervention. Samples from the hippocampus, cortex and hypothalamus were obtained at 79PND. The global DNA methylation profile was assessed using an ELISA-based method and the expression of Dnmt1 was evaluated by real-time PCR. Significantly increased methylation was observed in the hypothalamus of animals from the EX group in comparison to CTL. Comparative analysis involving the EX-ST and ST groups revealed increased global DNA methylation in the hippocampus, cortex, and hypothalamus of EX-ST, indicating the potential of physical exercise in modulating the responses evoked by RRS. Furthermore, decreased expression of the Dnmt1 gene was observed in the hippocampus and hypothalamus of animals from the EX-ST group. In summary, our data indicate that physical exercise affects DNA methylation of the hypothalamus and might modulate epigenetic responses evoked by RRS in the hippocampus, cortex, and hypothalamus. Copyright © 2015. Published by Elsevier B.V.
    Behavioural brain research 09/2015; 296. DOI:10.1016/j.bbr.2015.08.038 · 3.03 Impact Factor
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    • "Exercise is another preventive measure that has been shown to modulate the expression of genes regulating the methylation and acetylation of DNA and protein. Studies have shown decreased expression of DNA methyltransferases [118] and increased expression of HAT [119] in the hippocampus of rats which exert their epigenetic influence by increasing the expression of neurotrophic factors in brain. Further evidence was provided by Scopel et al.[120] by showing that exercise regime of 20 minutes for 2 weeks for wistar rat attenuates the damage in hippocampal slices submitted to ischemia in-vitro opening the field for further investigation. "
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    ABSTRACT: Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and retinal degeneration have been studied extensively and varying molecular mechanisms have been proposed for onset of such diseases. Although genetic analysis of these diseases has also been described, yet the mechanisms governing the extent of vulnerability to such diseases remains unresolved. Recent studies have, therefore, focused on the role of environmental exposure in progression of such diseases especially in the context of prenatal and postnatal life, explaining how molecular mechanisms mediate epigenetic changes leading to degenerative diseases. This review summarizes both the animal and human studies describing various environmental stimuli to which an individual or an animal is exposed during in-utero and postnatal period and mechanisms that promote neurodegeneration. The SNPs mediating gene environment interaction are also described. Further, preventive and therapeutic strategies are suggested for effective intervention.
    Translational Neurodegeneration 04/2014; 3(1):9. DOI:10.1186/2047-9158-3-9
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    ABSTRACT: Significant progress has been made in understanding the neurobiological mechanisms through which exercise protects and restores the brain. In this feature review, we integrate animal and human research, examining physical activity effects across multiple levels of description (neurons up to inter-regional pathways). We evaluate the influence of exercise on hippocampal structure and function, addressing common themes such as spatial memory and pattern separation, brain structure and plasticity, neurotrophic factors, and vasculature. Areas of research focused more within species, such as hippocampal neurogenesis in rodents, also provide crucial insight into the protective role of physical activity. Overall, converging evidence suggests exercise benefits brain function and cognition across the mammalian lifespan, which may translate into reduced risk for Alzheimer's disease (AD) in humans.
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