Neuropsychopathology And Neurobehavioral Characteristics of PPA-Induced Autism Like Rat Model and Its Correlation with Gut-Brain Dysbiosis Occurring in Autism Spectrum Disorder

Abstract: Autism Spectrum Disorder (ASD) involves social interaction deficit, impaired communication skills, and pervasive and stereotypic behavior. It also involves co-morbidities such as anxiety, aggressive nature, and epilepsy. Apart from the above, this disorder also affects physiological co-morbidities that co-exist with behavioral symptoms, such as immune system and mitochondrial dysfunction, and gastrointestinal complications, leading to oxidative stress neuroinflammation, further worsening the behavioral complications. It has been reported that 23%-70% of patients who have ASD account for gastrointestinal complications, which correlate with behaviors relevant to autistic endophenotype. A strong gut-brain dysbiosis occurs in ASD patients due to the enormous production of short-chain fatty acids such as propanoic acid (PPA) by abnormal gut-flora, worsening the behavioral neurochemical and mitochondrial dysfunction. This further leads to the generation of free radical species responsible for synthesizing pro-inflammatory cytokines, which cause microglia activation. There are various animal models of autism, such as the induced animal model and transgenic animal model, which could give valuable hints toward understanding the molecular, cellular, and pathomorphological processes involved in this neurodevelopmental disorder heterogeneous and has a multifactorial origin. However, though all animal models focus on establishing the face validity of ASD, very few focus on construct validity and predictive validity about gut-brain dysbiosis in ASD patients because of the abnormal gut-flora leaky-gut phenomenon. Thus, in this chapter, our focus would be to understand the phenomenon of gut-brain cross-talk in ASD, the role of short-chain fatty acids, and to bring forth the neuropsychopathology of propanoic acid (PPA)-induced rat model of ASD, which can help in establishing construct as well as predictive validity with the gut-brain cross-talk and the neuroimmune as well as behavioral complications occurring as a result of short-chain fatty acids and abnormal gut flora.

Keywords: Autism, Gut-microbiota, Inflammatory cytokines, Neurobehavior, Propanoic acid.