Research ArticlePrenatal and Postnatal Epigenetic Programming: Implications for GI, Immune, and Neuronal Function in Autism
Mostafa I. Waly,1 Mady Hornig,2 Malav Trivedi,3 Nathaniel Hodgson,3 Radhika Kini,3 Akio Ohta,3 and Richard Deth31Department of Food Science and Nutrition, Sultan Qaboos University, Alkoudh 123, Muscat, Oman
2Department of Epidemiology, Columbia University, New York, NY 10032, USA
3Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USAReceived 23 January 2012; Accepted 3 May 2012Academic Editor: Antonio M. Persico Copyright © 2012 Mostafa I. Waly et al.
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Although autism is first and foremost a disorder of the central nervous system, comorbid dysfunction of the gastrointestinal (GI) and immune systems is common, suggesting that all three systems may be affected by common molecular mechanisms.
Substantial systemic deficits in the antioxidant glutathione and its precursor, cysteine, have been documented in autism in association with oxidative stress and impaired methylation.
DNA and histone methylation provide epigenetic regulation of gene expression during prenatal and postnatal development. Prenatal epigenetic programming (PrEP) can be affected by the maternal metabolic and nutritional environment, whereas postnatal epigenetic programming (PEP) importantly depends upon nutritional support provided through the GI tract. Cysteine absorption from the GI tract is a crucial determinant of antioxidant capacity, and systemic deficits of glutathione and cysteine in autism are likely to reflect impaired cysteine absorption. Excitatory amino acid transporter 3 (EAAT3) provides cysteine uptake for GI epithelial, neuronal, and immune cells, and its activity is decreased during oxidative stress.
Based upon these observations, we propose that neurodevelopmental, GI, and immune aspects of autism each reflect manifestations of inadequate antioxidant capacity, secondary to impaired cysteine uptake by the GI tract.
Genetic and environmental factors that adversely affect antioxidant capacity can disrupt PrEP and/or PEP, increasing vulnerability to autism.
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