Evaluating the impact of valproic acid and valpromide on histone acetylation and the development of ASD-like traits in zebrafish models

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Haven Henry¹, Dr. Denise Flaherty¹; ¹Eckerd College

The role of histone acetylation on the onset of autism spectrum disorder (ASD) provides important insights into the epigenetic mechanisms underlying neurodevelopmental conditions. Prenatal environmental factors, such as altered histone deacetylase (HDAC) activity, suggest that variations in histone acetylation may contribute to the onset of ASD. Maternal use of the anti-epileptic drug valproic acid (VPA) during pregnancy has been associated with ASD-like behaviors and physical malformations in children. In contrast, valpromide (VPD), a structural analog of VPA, does not inhibit HDACs. Despite this distinction, few studies have examined histone acetylation levels as a potential regulatory mechanism for these effects. This study investigates zebrafish (Danio rerio) physical and behavioral development during larval and adult stages following exposure to VPA and VPD at 5-7 hours post-fertilization (hpf). Histone acetylation levels will be measured in embryos (24 hpf, 48 hpf), larvae (7 dpf), and adults (30 dpf). Physical malformations (e.g., body length, pericardial edema, swim bladder development, spinal curvature) and behavioral traits (e.g., shoaling, social contact, swimming speed, distance traveled, thigmotaxis) will be evaluated in larvae and adults. The results are expected to show more physical malformations, behavioral impairments, and higher histone acetylation levels in VPA-treated zebrafish compared to the VPD group. By comparing the effects of VPA with VPD, this research aims to reveal how these compounds influence ASD development. A better understanding of VPA’s mechanisms could encourage physicians to carefully weigh its side effects, including the risk of ASD, and opt for safer alternatives when prescribing medications.

Topic Area: EMOTION & SOCIAL: Development & aging