Environmental Enrichment Modified Epigenetic Mechanisms in SAMP8 Mouse Hippocampus by Reducing Oxidative Stress and Inflammaging and Achieving Neuroprotection

Abstract

With the increase in life expectancy, aging and age-related cognitive impairments are becoming one of the most important issues for human health. At the same time, it has been shown that epigenetic mechanisms are emerging as universally important factors in life expectancy. The Senescence Accelerated Mouse P8 (SAMP8) strain exhibits age-related deterioration evidenced in learning and memory abilities and is a useful model of neurodegenerative disease. In SAMP8, Environmental Enrichment (EE) increased DNA-methylation levels (5-mC) and reduced hydroxymethylation levels (5-hmC), as well as increased histone H3 and H4 acetylation levels. Likewise, we found changes in the hippocampal gene expression of some chromatin-modifying enzyme genes, such as Dnmt3b. Hdac1. Hdac2. Sirt2, and Sirt6. Subsequently, we assessed the effects of EE on neuroprotection-related transcription factors, such as the Nuclear regulatory factor 2 (Nrf2)–Antioxidant Response Element pathway and Nuclear Factor kappa Beta (NF-κB), which play critical roles in inflammation. We found that EE produces an increased expression of antioxidant genes, such as Hmox1. Aox1, and Cox2, and reduced the expression of inflammatory genes such as IL-6 and Cxcl10, all of this within the epigenetic context modified by EE. In conclusion, EE prevents epigenetic changes that promote or drive oxidative stress and inflammaging.

Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

“…Consistent with this, CMS promoted an increase in the pro-oxidant enzyme Aox1 gene expression and higher accumulation of ROS. Noteworthy, as described, differences between strains were found in most of the markers evaluated [4].…”

“…This last process is due to histone deacetylases (HDAC) enzymes. Deregulation of histone acetylation has been related to an increase of the risk of age-dependent memory impairment in mice [4,26,27]. Specifically, histone H4 lysine 12 acetylation alterations causes impaired memory consolidation as well as its restoration reinstates the expression of learning-induced genes and in consequence, cognitive abilities [26].…”

“…Aging is the most significant risk factor for most chronic diseases, such as age-related cognitive decline and Alzheimer's disease (AD) [3]. In fact, AD is the most prevalent dementia and its progression is influenced by both genetic and environmental factors [4].Several studies define that a good environment is essential to enhance learning and cognitive abilities, besides the continued presence of stressors being associated with the opposite effects. Epigenetics refers to potentially heritable and environmentally modifiable changes in gene expression mediated via non-DNA encoded mechanisms [5].…”

“…Aging is the most significant risk factor for most chronic diseases, such as age-related cognitive decline and Alzheimer's disease (AD) [3]. In fact, AD is the most prevalent dementia and its progression is influenced by both genetic and environmental factors [4].…”

Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice

“…Certainly, epidemiological studies show that those living in a lower socioeconomic environments are more likely to be impacted by harmful alcohol consumption and/or obesity (Batty, Lewars, Emslie, Benzeval, & Hunt, 2008;McCartney et al, 2016;Ferraro, Schafer, & Wilkinson, 2016;Non et al, 2016). While the mechanisms underlying the detrimental neural effects of ethanol and sucrose remain unclear, the provision of environmental enrichment has been shown to be neuroprotective in rodents (Anastasía, Torre, de Erausquin, & Mascó, 2009;Barone, Novelli, Piano, Gargini, & Strettoi, 2012;Griñan-Ferré et al, 2016;Kiss et al, 2013;Livingston-Thomas et al, 2016).…”