Daniel Reddin, “Adolescent Stress-Induced Social Deficits are Influenced by Histone Acetylation”
Mentor: Polymnia Georgiou, Psychology, Letters & Science (College of)
Poster #155
Autism spectrum disorder (ASD) is a spectrum of neurodevelopmental disorders impacting 1 in 36 children in the United States. ASD is typically diagnosed during adolescence. Adolescence is a developmental period characterized by an increase in gonadal hormones production, thus it can be postulated that this spike in gonadal hormones may be the underlying factor for the increased incidence of ASD. Further supporting a hormone related mechanism is that the prevalence of ASD is higher in males compared with females with a ratio of 4:1. Interestingly, estrogen receptor beta (ERβ) has found to be related with this sex specific difference with lower levels of ERβ found in people with ASD. Thus, we hypothesized that the gonadal hormone estradiol and its receptor, ERβ are important regulators for the development of ASD-related symptoms including social and anxiety deficits especially following an environmental trigger like stress. To test this, we first investigated the development of social and anxiety deficits following stress in adolescent males and females. We show that following acute stress both male and female adolescent mice developed social deficits, an effect not observed in adult mice demonstrating specificity to adolescence. Drug repurposing screening from RNA-seq data in human adolescents with social deficits, showed that histone deacetylase inhibitors reverse the molecular changes observed. To validate this in our model, we demonstrated that HDAC inhibitors can reverse social deficits and protect from the development of anxiety like behaviors during adulthood. Altogether this data suggests that histone acetylation changes effect gene expression resulting social deficits. Future studies will investigate whether these acetylation changes prevent ERβ binding on the DNA thus contributing to the hormone related gene expression changes resulting in ASD-related symptoms.