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Epigenetic change triggers "ADHD brake" in rats
October 23, 2015

One of the best known examples of early childhood epigenetic imprinting of personality is seen in the offspring of “non-licking” rats. If the mothers of newborn rats give minimal attention to their offspring (e.g. they do not lick them enough), the gene of glucocorticoid receptor, an important stress hormone receptor in the hippocampus, is insufficiently released from methyl groups. In this scenario, these epigenetic barriers remain, and the rats express low levels of stress hormone receptors for life, causing chronic hypersensitive stress regulation.

Recently, researchers in the United States have found that similar epigenetic processes in rats may be involved in the onset of behavioural disorders such as attention deficit hyperactivity disorder (ADHD), autism, and schizophrenia. These epigenetic changes occur in a different region of the brain and involve the gene of another receptor. If these processes are confirmed to occur in humans, it would imply that epigenetic changes at birth influence the risk of a number of psychiatric disorders later during life. 

Stacey Kigar and colleagues epigenetically inhibited (via siRNA) the production of Gadd45b protein in the amygdala (the fear center of the brain) in rats immediately after birth. It is believed that Gadd45b supports cells in the active removal of methyl groups from DNA. If this this mechanism is missing, cells do not succeed in reactivating the epigenetically inactivated genes. 

At the age of three weeks, which corresponds to childhood in humans, the treated rats exhibited pronounced anxiety and juvenile social play behaviour that can be best described as rat ADHD. At the same time, a few genes that are known to play a role in psychiatric disorders when disregulated were less active than normally expected in the animals. Moreover, the gene for a receptor called Adra2a was significantly suppressed by DNA methylation. This receptor is a docking site that is activated by the ADHD drug Ritalin, which means that it acts as a brake for excessive social play behaviour. The animals that had very few of these receptors particularly exhibited more active behaviour. 

The epigenetically active substance Gadd45b "plays until now an unknown role in the organization of social behaviour in the amygdala," wrote Kigar, in an article for the Internet site EpiBeat. Although the researchers discovered this phenomenon in a laboratory setting, it is plausible that environmental factors such as lack of attention to offspring would have comparable effects outside of the laboratory.

Source: http://www.newsletter-epigenetik.de/