The Resemblance between the Propionic Acid Rodent Model of Autism and Autism Spectrum Disorder
Abstract:
Autism spectrum disorder is a complex, lifelong, heterogeneous, multi-factorial developmental disability with a dynamic set of metabolic, mitochondrial, immune, neuroinflammatory, and behavioral abnormalities affecting several body parts. Autism Spectrum Disorder (ASD) is manifested by cognitive, behavioral, and social deficits with early childhood onset. Appropriate animal models that can mimic core symptoms of Autism are difficult to develop, although essential to explore the pathogenesis of ASD and discover potential medicines useful in this disorder. Propionic acid (PPA) is an intermediary product of cellular fatty acid metabolism found in the gut. Furthermore, PPA is an end product produced by the intestinal tract, skin, and oral mucosa bacteria. In addition to its endogenous synthesis, PPA is naturally present in various foodstuffs as a preferred preservative. Although PPA may be beneficial at appropriate levels, excessive PPA appears to have some adverse effects on health and behavior. PPA can readily cross the gut-blood, blood-brain, and placental barriers. PPA particularly gets concentrated intracellularly, producing deleterious effects on the developing brain. This becomes noteworthy in the context of ASD since PPA affects cell signaling, neurotransmitter synthesis, mitochondrial function, lipid metabolism, immune function, neuroinflammation, and gene expression. After administration of PPA by different routes in rodents, the observations suggest that PPA may be linked to the behavioral, neuropathological, and biochemical abnormalities observed in ASD. There is a possibility that Propionic acid could be the intrauterine candidate responsible for causing harm to the unborn child, resulting in the development of autism-like disorder. This review article elucidates a complete picture of Propionic acid's effects and mechanism of action when administered to rodents. The authors have examined the validity and utility of the PPA model of Autism in this review article. A thorough analysis of the data available in the literature from preclinical studies as well as the clinical reports justifies the utility of the PPA rodent model of Autism as a tool in neurochemistry and experimental pharmacology.
