Developmental Neuroscience

Epigenetics

Epigenetics is the study the interaction between genes and the environment, and the changes in expression of genes caused by experiences with the environment. The work ‘epigenesis’ was used by Aristotle to describe a process explaining how are individual characteristics come into being [1]. The mechanisms by which epigenetics operates involves histone molecule acetylation and methylation, which effectively turn on and off segments of DNA, respectively. These epigenetic mechanisms interact with the environment, and can play an important role in neurodevelopmental reprogramming (altering the development of the brain) [2].

In animals, differing phenotypes can be due to epigenetic mechanisms. For example, dietary changes in the form of supplementation of methyl groups given to pregnant mice of a specific strain causes pups to develop coat color changes and healthy or unhealthy constitutions [3].

Consider the calico cat. Early in female mammal embryo development, epigenetic processes inactivate one of the X chromosomes in cells at random, so X chromosomes in each cell can be different [1]. The calico cat shows this randomization in the color of their coats, reflecting some X chromosomes from both her mother and father having been randomly inactivated, and is a trait that is stable over her lifetime.

In humans, the interaction between genetics and the environment is an important consideration for determining the risk for and trajectory of complex neurodevelopmental disorders (NDDs) like autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) [4]. The phenotypic heterogeneity in these NDDs is determined by the interaction between genetic susceptibility and exposure to environmental risk factors (like chemicals, maternal infection or disease, radiation, or other teratogens), as well as the timing of the teratogen exposure.

Interestingly, the effects of epigenetics can be transgenerational, passing from parent to offspring through the reprogramming of germ cells [4]. These transgenerational effects can depend on whether the mother or father has the trait and whether male or female offspring inherit the trait. For example, exposure to environmental factors like famine can cause prepubescent boys to have children and grandchildren who are more susceptible to certain diseases [5].

[1] Moore, D. S. (2017). Behavioral epigenetics. Wiley Interdisciplinary Reviews. Systems Biology and Medicine, 9(1), doi:10.1002/wsbm.1333

[2] Bale, T. L. (2015). Epigenetic and transgenerational reprogramming of brain development. Nature Reviews. Neuroscience, 16(6), 332-344. doi:10.1038/nrn3818

[3] Cropley, J. E., Dang, T. Y., Martin, D. K., & Suter, C. M. (2012). The penetrance of an epigenetic trait in mice is progressively yet reversibly increased by selection and environment. Proceedings. Biological Sciences, 279(1737), 2347-2353. doi:10.1098/rspb.2011.2646

[4] Lein, P. J. (2015). Overview of the Role of Environmental Factors in Neurodevelopmental Disorders. In Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders (pp. 3-20). Elsevier Inc. doi: 10.1016/B978-0-12-800228-5.00001-7

[5] Kaati, G., Bygren, L. O., & Edvinsson, S. (2002). Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. European Journal Of Human Genetics: EJHG, 10(11), 682-688.

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