Abstract
Autism Spectrum Disorder (ASD) affects an estimated 21.7 million individuals globally with an estimated annual cost to the United States of $35 billion. Manifestations of ASD present across a spectrum and its etiology derives from numerous factors such as Valproic Acid (VPA), a drug used for multiple medicinal purposes. Rat pups born of dams treated with VPA during gestation exhibit behavior and neuronal morphologies consistent with ASD and therefore represent a strong candidate for ASD investigation. Our original study proposed to investigate the effects of Medial Ganglionic Eminence (MGE) progenitor cell treatment on rat pups with ASD induced by VPA and hypothesized amelioration of symptoms facilitated by integration of MGE cells. However, due to amendments to the protocol required by the Institutional Animal Care and Use Committees (IACUC), the study was redirected to investigate the effects of VPA on progenitor cells derived from the MGE and subsequent behavioral changes. Stereology, behavior assessment, tissue histology, immunostaining, and visual assessment of neuronal morphology was used to this end. The specific aim of this investigation is quantification of Parvalbumin, Calretinin, and Calbindin expressing interneurons within the cortex of the rat brain and assessment of behavioral changes after treatment with VPA. We hypothesize a reduction in all three interneuron subtypes as well as changes toward stereotypical ASD behaviors owing to the number of progenitor cells present at the time of insult. Results supporting this hypothesis have the potential to contribute to the discovery of a cure to ASD, which is of significance because currently there are only treatments available for ASD. This project occurred at Shriners Hospital for Children from June 1, 2016 to January 31, 2017.