Effects of traumatic stress in adolescence on PTSD-like behaviors, dendrite development, and H3K9me2/BDNF expression in the amygdala of male rats

Abstract

Early detrimental experiences increase the risk of psychiatric disorders, including posttraumatic stress disorder (PTSD). In a previous experiment, we demonstrated that traumatic stress in adolescence triggers changes in the expression of the epigenetic marker H3K9me2 in the hippocampus and prefrontal cortex of adolescent and adult rats, which suppresses transcription of the brain-derived neurotrophic factor (Bdnf) gene that promotes dendrite development and synaptic growth. However, corresponding changes in the amygdala in response to traumatic stress in early life have not yet been fully elucidated. In the current study, we used the inescapable foot shock (IFS) procedure to establish a PTSD model. Half an hour after the end of electric shocks, intraperitoneal injection of the G9a enzyme inhibitor Unc0642, a small molecule inhibitor of EHMT2 that can decrease H3K9me2 expression, was applied to reverse the corresponding epigenetic changes. Exploratory behaviors, anxiety-like behavior, social communication ability, spatial exploration and memory were determined using the open field test (OFT), elevated plus maze (EPM) test, three-chamber sociability test (SIT), Morris water maze (MWM) test, and Y maze test (YMZ), respectively. Additionally, the levels of H3K9me2 and BDNF were measured by quantitative reverse transcription-polymerase chain reaction (qPCR) and Western blotting. Furthermore, neuronal development was examined using Golgi staining. The results showed that the IFS procedure induced anxiety-like and depression-like behaviors, social skills dysfunction, and spatial exploration and memory disorders. It also decreased the mRNA expression of BDNF and BDNF and increased the expression of H3K9me2 in the amygdala. More importantly, compared to unstressed animals, traumatic stress during adolescence induced dendrite maldevelopment in adolescent and adult rats. In summary, the present study indicates that early-life stress alters the epigenetic marker expression of H3K9me2 and decreases levels of BDNF in the amygdala, resulting in dendrite maldevelopment and a higher risk of mental disorders.

Keywords: Amygdala; BDNF; Dendrite development; H3K9me2; PTSD.