Poster Title

Evaluating sex differences and the effect of perinatal testosterone in the VPA mouse model of autism

Grade Level at Time of Presentation

Senior

Institution

University of Louisville

KY House District #

40

KY Senate District #

40

Department

Biology Department

Abstract

Autism spectrum disorder (ASD) is more common in males than females, but the mechanism of this bias remains unknown. Elevated levels of fetal testosterone (fT) have been correlated with ASD diagnosis. Valproic acid (VPA), an antiepileptic medication, increases ASD risk in humans when used during pregnancy. The VPA rodent model of ASD mimics many of the behavioral and morphological features of ASD, with male rodents more vulnerable to some VPA effects. We used this model to test differential susceptibility by sex to prenatal insult (VPA), and to determine whether masculinizing females perinatally with testosterone propionate (TP) following prenatal VPA treatment would also masculinize their risk for abnormalities in ASD-related brain development and behavior. We demonstrated that VPA exposure in utero resulted in both delayed maturation and regression of skill development in motor development tests. In addition, VPA-TP males appeared to have reduced anxiety in the elevated plus maze, as measured by increased frequency and duration of open arm entries and the shortest duration in the closed arms, while displaying the highest velocity. In the wheel running assay all mice displayed normal routine gaining and cognitive rigidity; however, females, regardless of treatment group, displayed higher sociability as measured by time spent following a novel mouse. Finally, we found that cerebellum volume was unrelated to treatment group. Our study supports previous findings that prenatal VPA treatment impacts motor development; however, we did not find major effects of sex on vulnerability to VPA treatment or an effect of perinatal testosterone.

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Evaluating sex differences and the effect of perinatal testosterone in the VPA mouse model of autism

Autism spectrum disorder (ASD) is more common in males than females, but the mechanism of this bias remains unknown. Elevated levels of fetal testosterone (fT) have been correlated with ASD diagnosis. Valproic acid (VPA), an antiepileptic medication, increases ASD risk in humans when used during pregnancy. The VPA rodent model of ASD mimics many of the behavioral and morphological features of ASD, with male rodents more vulnerable to some VPA effects. We used this model to test differential susceptibility by sex to prenatal insult (VPA), and to determine whether masculinizing females perinatally with testosterone propionate (TP) following prenatal VPA treatment would also masculinize their risk for abnormalities in ASD-related brain development and behavior. We demonstrated that VPA exposure in utero resulted in both delayed maturation and regression of skill development in motor development tests. In addition, VPA-TP males appeared to have reduced anxiety in the elevated plus maze, as measured by increased frequency and duration of open arm entries and the shortest duration in the closed arms, while displaying the highest velocity. In the wheel running assay all mice displayed normal routine gaining and cognitive rigidity; however, females, regardless of treatment group, displayed higher sociability as measured by time spent following a novel mouse. Finally, we found that cerebellum volume was unrelated to treatment group. Our study supports previous findings that prenatal VPA treatment impacts motor development; however, we did not find major effects of sex on vulnerability to VPA treatment or an effect of perinatal testosterone.