Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: A preliminary study.
ABSTRACT 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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ABSTRACT: Chromatin modifying enzymes DNA methyltransferases (DNMTs), histone deacetylase (HDAC) 2 and CREB binding protein (CBP) play a crucial role in memory, particularly during consolidation process which declines with advancing age. However, the expression of these enzymes and their effect on memory consolidation during aging are not clearly understood. In the present study, novel object recognition test was used to assess the memory consolidation followed by expression analysis of DNMTs, HDAC2 and CBP in the cerebral cortex and hippocampus of young, adult and old male mice. Object recognition memory was reduced in old as compared to young and adult. DNMT1 protein expression was high in the cerebral cortex and hippocampus of young male mice, but declined gradually with age. On the other hand, HDAC2 mRNA and protein expression increased in the hippocampus of old male mice as compared to young and adult. Alteration in the expression of these enzymes is correlated with reduced recognition memory in old.Biogerontology 06/2014; 15(4). · 3.01 Impact Factor
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ABSTRACT: Dynamic regulation of chromatin structure in postmitotic neurons plays an important role in learning and memory. Methylation of cytosine nucleotides has historically been considered the strongest and least modifiable of epigenetic marks. Accumulating recent data suggest that rapid and dynamic methylation and demethylation of specific genes in the brain may play a fundamental role in learning, memory formation, and behavioral plasticity. The current review focuses on the emergence of data that support the role of DNA methylation and demethylation, and its molecular mediators in memory formation.Dialogues in clinical neuroscience 09/2014; 16(3):359-71.
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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. 01/2014; 3:9.