Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder

Recent evidence suggests that a variety of environmental factors, including dietary and gastrointestinal agents, may contribute to autism spectrum disorders (ASD). Here we administered propionic acid (PPA), a short chain fatty acid that is used as a food preservative and also is a metabolic end-product of enteric bacteria in the gut, to adolescent (41 ± 4 days) male rats in a study of restricted/repetitive behavior, social behavior, and cognition. The goal was to further evaluate the effects of PPA in young rodents. PPA (4 μl of 0.26 M solution) was administered intracerebroventricularly prior to each behavioral test. Rats treated with PPA displayed restricted behavioral interest to a specific object among a group of objects, impaired social behavior, and impaired reversal in a T-maze task compared to controls given phosphate buffered saline. Immunohistochemical analysis of brain tissue from PPA rats revealed reactive astrogliosis and activated microglia, indicating an innate neuroinflammatory response.These findings are consistent with our earlier findings of ASD-relevant behavioral and brain events in adult rats given PPA, and support further study of effects of PPA in young rodents by establishing similar effects in adolescent animals.

Research highlights▶ Effects of propionic acid (ICV) in an adolescent rat model of ASD were studied. ▶ Propionic acid increased restricted/repetitive behavior toward objects. ▶ Propionic acid impaired social behavior in a novel rat–novel object choice test. ▶ Propionic acid impaired reversal learning, but not acquisition, in a T-maze. ▶ Results broaden the relevance of the propionic acid rat model of ASD.