Master of Science
Dr. Peter Ossenkopp
Dr. Martin Kavaliers
Research suggests that certain gut and dietary factors may worsen symptoms in autism spectrum disorder (ASD). Studies have shown that treatment with the bacterial product, propionic acid (PPA), elicits neuroinflammatory and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute. However, most studies of ASD, including those involving PPA, focus on males. The present study explored putative sex differences in the effects of PPA (500mg/kg) on a rat behavioral ASD phenotype and the influence of the estrous cycle and fluctuations in estradiol and progesterone. This was accompanied by examinations of the effects of ovariectomy and hormone replacement therapy with estradiol and progesterone. PPA produced no sex-differential effects, and elevated hormonal levels did not seem to play a protective role against the adverse effects of PPA.
Summary for Lay Audience
Autism spectrum disorder (ASD) refers to a broad range of conditions affecting brain development. Males are diagnosed four times more often than females, but the factors that explain this majority of males are generally unknown (Amaral, Schumann, & Nordahl, 2008; Beggiato et al., 2017; Zablotsky et al., 2015). One’s environment and genetics have been suggested to contribute to the expression of autism symptoms, however there is no single known cause for ASD (Zablotsky et al., 2015). Results from scientific studies have suggested that female hormones may provide protection against the expression of several symptoms of ASD. Autism has been said to be primarily a disorder of brain function, but issues with other bodily systems have become of interest. Of particular interest to the present study are issues with the gastrointestinal system, which appear to be very common in children diagnosed with ASD (Quigley & Hurley, 2000).Elevated levels of a bacteria, termed Clostridia, have been detected in the gastrointestinal tract of children with ASD. Clostridia produces short-chain fatty acids, one of which is known as Propionic Acid (PPA), which at high enough levels has been found to worsen ASD-like behavior in rodents. In this thesis, a PPA rat model for autism was used to study the influence of sex and female sex hormones on social behavior and anxiety. Research studies seeking to explore the effects of PPA in relation to ASD have explored these effects in males, and results from these studies are then generalized to both sexes. It is imperative that research continues to extend these studies to female populations. Findings from the current thesis do not suggest that higher levels of female sex hormones protect against the ASD-like behavioral effects of PPA.
Benitah, Katie C., "Characterizing putative sexually dimorphic effects of a propionic acid induced autism spectrum disorder phenotype in adult male and female rats" (2020). Electronic Thesis and Dissertation Repository. 7028.