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Sex differences in Autism Spectrum Disorder (ASD) are well documented; males are diagnosed 4:1 over females. Testosterone (T) is one factor that differs by sex in humans and mice that could increase vulnerability to developing ASD in males. Valproic acid (VPA) is an anticonvulsant that has been found to increase the risk of autism in male offspring of pregnant women who take it to control seizures and is commonly used in mouse models of ASD. After prenatal VPA or vehicle on embryonic day 13, testosterone (T) or vehicle was administered to the mice on postnatal day 2 to investigate whether it increased the vulnerability of mice to have autism-like behavior or neuroanatomical differences. This design produced three factors (prenatal VPA, postnatal T, and sex), which in combination produced eight treatment groups and can also be analyzed categorically on a scale of 0 – 3 as “hits”, in which VPA, T, and maleness are each considered a hit. As a small part of a larger project, I measured the cell area and linear cell density of Purkinje cells found in lobe 9 of the cerebellum at postnatal day 31. The neuroanatomical results were analyzed statistically using One-Way ANOVAs for treatment group and number of hits, which indicated that there were no significant differences in linear density or average cell area by treatment group or by number of hits. The larger project found some differences in behavior due to VPA treatment and that varied by number of hits.

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autism; valproic acid; testosterone; purkinje cells; cerebellum; triple hit hypothesis


Animal Studies | Cells | Medicine and Health Sciences | Neurosciences

Examining neuroanatomical effects of prenatal valproic acid and postnatal testosterone in a mouse model of autism spectrum disorder