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Choline and the Brain: An Epigenetic Perspective

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The Benefits of Natural Products for Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 12))

Abstract

Choline is an essential nutrient that is required for normal development of the brain. Via its metabolite betaine, it participates in the synthesis of S-adenosylmethionine, a major methyl donor for histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and may alter brain function. Besides its role in methyl group metabolism, choline also has pivotal functions, including the maintenance of structural integrity of membranes and modulation of cholinergic neurotransmission, functions that are often dysregulated in some neurodegenerative disorders. Emerging evidence suggests that environmental factors, including lifestyle or diet, sometimes cause epigenetic changes in the expression of neuronal genes resulting in long-term changes in brain function. Recently, choline has been implicated as an epigenetic modifier of the genome that may alter gene methylation, expression, and cellular function. Abnormal level of choline during fetal or early postnatal life has been shown to alter memory functions during adulthood. It may also contribute to the etiology of stress-related disorders and age-related decline in memory later in life. Conversely, rodent studies suggested that perinatal choline supplementation enhances performance in memory-related tasks during adulthood. In this chapter, we will focus on the impact of choline-gene interaction on brain function in early life and during adulthood. In particular, we will emphasize the potential role of choline as a neuroprotectant that may mitigate some of the adverse effects of neurodegenerative disorders and protect mental health across the lifespan.

An erratum to this chapter can be found at http://dx.doi.org/10.1007/978-3-319-28383-8_24

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Abbreviations

Ach:

Acetylcholine

AchE:

Acetylcholine esterase

APP:

Amyloid precursor protein

ChAT:

Choline acetyltransferase

Dnmts:

DNA methyltransferases

E:

Embryonic day

HDACs:

Histone deacetylases

HMTs:

Histone methyltransferases

HPA:

Hypothalamic-pituitary-adrenal

IGF:

Insulin-like growth factor

5MTHF:

5-Methyltetrahydrofolate

MTHFR:

Methyltetrahydrofolate reductase

NPC:

Neural progenitor cell

PC:

Phosphatidylcholine

PEM:

Phosphatidylethanolamine

POMC:

Proopiomelanocortin

RE1:

Repressor element-1

SAH:

S-Adenosylhomocysteine

SAM:

S-Adenosylmethionine

THF:

Tetrahydrofolate

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  1. Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA

    Rola Aldana Bekdash

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  1. Rola Aldana Bekdash
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  1. Food Science and Nutrition College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, Oman

    M. Mohamed Essa

  2. National Institutes of Health, National Institute on Alcohol Abuse, Rockville, Maryland, USA

    Mohammed Akbar

  3. Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia

    Gilles Guillemin

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Bekdash, R.A. (2016). Choline and the Brain: An Epigenetic Perspective. In: Essa, M., Akbar, M., Guillemin, G. (eds) The Benefits of Natural Products for Neurodegenerative Diseases. Advances in Neurobiology, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-28383-8_21

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