The enteric metabolite, propionic acid, impairs social behavior and increases anxiety in a rodent ASD model: Examining sex differences and the influence of the estrous cycle

• Published in: Pharmacology, biochemistry and behavior Vol. 231; p. 173630
• Main Authors: Benitah, Katie C., Kavaliers, Martin, Ossenkopp, Klaus-Peter
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2023
• Subjects: Anxiety; Estradiol; Estrous cycle; Gut microbiome; Progesterone; Rat; Sex differences; Short-chain fatty acid; Social behavior; Social behavior; Rat; Short-chain fatty acid; Sex differences; Anxiety; Progesterone; Estrous cycle; Gut microbiome; Estradiol
• ISSN: 0091-3057; 1873-5177; 1873-5177
• DOI: 10.1016/j.pbb.2023.173630

Research suggests that certain gut and dietary factors may worsen behavioral features of autism spectrum disorder (ASD). Treatment with propionic acid (PPA) has been found to create both brain and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in human ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute to this bias. The majority of PPA studies in relation to ASD focus on male subjects; research examining the effects of PPA in females is scarce. The present study includes two experiments. Experiment 1 explored sex differences in the effects of systemic administration of PPA (500 mg/kg, ip) on adult rodent social behavior and anxiety (light-dark test). Experiment 2 investigated differential effects of systemic administration of PPA (500 mg/kg) on social behavior and anxiety in relation to fluctuating estrogen and progesterone levels during the adult rodent estrous cycle. PPA treatment impaired social behavior and increased anxiety in females to the same degree in comparison to PPA-treated males. As well, females treated with PPA in their diestrus phase did not differ significantly in comparison to females administered PPA in their proestrus phase, in terms of reduced social behavior and increased anxiety. •Systemic treatment with propionic acid (PPA) reduced social interaction and increased anxiety in adult rats.•PPA treatment reduced social interaction and increased anxiety to the same degree in males and females.•In female rats PPA treatment altered social behavior and anxiety to the same degree between proestrus and diestrus.