Abstract
The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS) and its regulation in diseases is one of the most interesting processes of contemporary neuroscience. In the last decade, a growing body of literature suggests that long-term changes in gene transcription associated with CNS’s regulation and neurological disorders are mediated via modulation of chromatin structure. “Epigenetics”, introduced for the first time by Waddington in the early 1940s, has been traditionally referred to a variety of mechanisms that allow heritable changes in gene expression even in the absence of DNA mutation. However, new definitions acknowledge that many of these mechanisms used to perpetuate epigenetic traits in dividing cells are used by neurons to control a variety of functions dependent on gene expression. Indeed, in the recent years these mechanisms have shown their importance in the maintenance of a healthy CNS. Moreover, environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A (acetyl-coA), nicotinamide adenine dinucleotide (NAD+) and beta hydroxybutyrate (β-HB), regulates some of these epigenetic modifications, linking in a precise way environment with gene expression. This manuscript will portray what is currently understood about the role of epigenetic mechanisms in the function and homeostasis of the CNS and their participation in a variety of neurological disorders. We will discuss how the machinery that controls these modifications plays an important role in processes involved in neurological disorders such as neurogenesis and cell growth. Moreover, we will discuss how environmental inputs modulate these modifications producing metabolic and physiological alterations that could exert beneficial effects on neurological diseases. Finally, we will highlight possible future directions in the field of epigenetics and neurological disorders.
Highlights
The role of epigenetic mechanisms in the function and homeostasis of the central nervous system (CNS) and its regulation in diseases is one of the most interesting processes of contemporary neuroscience
A growing body of literature suggests that long-term changes in gene transcription associated with CNS’s regulation and neurological disorders are mediated via modulation of chromatin structure
Environmental inputs that have shown effects in CNS diseases, such as nutrition, that can modulate the concentration of a variety of metabolites such as acetyl-coenzyme A, nicotinamide adenine dinucleotide (NAD+) and beta hydroxybutyrate (β-HB), regulates some of these epigenetic modifications, linking in a precise way environment with gene expression
Summary
Facultad de Medicina, Departamento de Fisiología, Universidad Nacional Autónoma de México, México, D.F., México. LINKING THE ENVIRONMENT, NUTRITION AND EPIGENETIC MODIFICATIONS many aspects of nutrition and different kinds of lifestyles influence metabolic status and disease trajectory throughout our life, emerging findings suggest that changing our metabolism with exercise or different dietary regimens such as ketogenic diets, low-carbohydrate diets, intermittent fasting or physical exercise can alter the concentration of a variety of metabolites, some of them capable of modulating the activity of proteins that elicit epigenetic modifications (Figure 1; Shimazu et al, 2013; Shyh-Chang et al, 2013) These epigenetic modifications seem to regulate important networks of genes mediating physiological processes associated with the beneficial effect of these diets, providing a rationale and simple way to prevent or even treat these diseases. These modifications are dynamic in the way that they are actively added and removed by histone-modifying enzymes in a site-specific manner, which is essential for coordinated transcriptional control
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