Propionic Acid Animal Model of Autism

Sandy Shultz, Derrick F. MacFabe

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review


Autism spectrum disorders (ASD) are an increasing problem in Western society. Although largely genetic in nature, many environmental factors may play a role in triggering ASD in sensitive populations. Early antibiotic exposure, systemic immune and metabolic abnormalities, food cravings, and gastrointestinal comorbidities, which often relate to behavioral worsening, have been observed. Consequently, there is a growing need to develop animal models to examine how environmental factors relate to ASD pathogenesis. While growing evidence suggests that dietary or gut-related factors may influence brain function and symptomology in ASD patients, until recently no specific compounds have been identified which could provide a common explanation for the behavioral, biochemical, and neuropathological changes observed in ASD. This chapter will describe the recently developed propionic acid (PPA) rodent model of ASD and how its findings may relate to the clinical condition. PPA is a short-chain fatty acid that is endogenous to the human body as both an intermediary of fatty acid metabolism and a fermentation end product of antibiotic resistant enteric gut bacteria such as clostridia. Although largely derived in the gut, PPA and related short-chain fatty acids can readily gain access to the brain, where they can induce a diverse range of neurophysiological processes capable of altering both brain function and behavior. There are numerous lines of evidence suggesting that PPA and other enteric short-chain fatty acids may be elevated in ASD. To further examine the relationship between PPA and ASD, intracerebroventricular (ICV) injections of PPA in rats have recently been used as an animal model of ASD. Studies using this model have found that ICV treatment of PPA is capable of inducing numerous behavioral, electrophysiological, and neuropathological changes in rats that are consistent with those observed in ASD. Similar, but less pronounced, effects are also induced by ICV treatment of related gut short-chain fatty acids such as butyrate and sodium acetate. Together these findings suggest PPA and related short-chain fatty acids as putative risk factors for ASD and provide further evidence for a possible link between diet, metabolic, and/or gastrointestinal factors and ASD.
Original languageEnglish
Title of host publicationComprehensive Guide to Autism
EditorsVinood B. Patel, Victor R. Preedy, Colin R. Martin
Place of PublicationNew York, NY
Number of pages24
ISBN (Electronic)9781461447887
ISBN (Print)9781461447870
Publication statusPublished - 2014
Externally publishedYes

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