Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats

Epigenetics is a gene-environment interaction mechanism, manifested mostly through changes in regulatory gene expression. Stress is an established environmental factor known to induce epigenetic changes. This study aimed to assess the long-term effect of stress as juveniles, or juvenile and adult stress, on alterations in glutamic acid decarboxylase genes (GAD65, GAD67). We assessed DNA methylation and RNA expression in four rat groups: (1) control group, (2) juvenile stress group sacrificed two days following stress exposure (JSe) (RNA only), (3) juvenile stress group sacrificed as adults (JS), and (4) juvenile and adult stress group (JS + AS). Three different areas of the brain were examined in each group: the dorsal dentate gyrus (dDG), the dorsal CA1 (dCA1), and the basolateral amygdala (BLA). A significantly low methylation level of GAD65 in the BLA was observed among the JS group, followed by almost complete recovery among the JS + AS group. However, in dDG, an opposite trend was captured, and higher GAD65 methylation was found in JS. In addition, RNA levels were found to be decreased in JS compared to JSe and JS + AS. These findings can point to a possible mechanism: while juvenile stress may enhance a better coping strategy with life challenges, additional stress in adulthood may trigger a contradictory response, either beneficial or harmful.