Pathophysiological and neurobehavioral characteristics of a propionic acid‐mediated autism‐like rat model

Abstract

Autism spectrum disorder (ASD) is induced by complex hereditary and environmental factors. However, the mechanisms of ASD development are poorly understood. The purpose of this study was to identify the standard indicators of this condition by comparing clinical, pathophysiological, and neurobehavioral features in an autism‐like animal model. A total of 22 male Sprague‐Dawley (SD) rats were randomly divided into control and 500 mg/kg propionic acid (PPA)‐treated groups. The rats were subjected to behavioral testing, gene expression, and histology were examined to detect pathophysiological and neurobehavioral alterations. Exploratory activity and non‐aggressive behavior were significantly reduced in PPA‐treated rats, whereas we observed enhanced aggressive behavior in terms of adjacent interactions on Day 14 after PPA treatment. To evaluate gene expression after PPA administration, we analyzed tissue from the hippocampus using reverse transcription polymerase chain reaction (RT‐PCR). Glial fibrillary acidic protein (GFAP) was augmented in the PPA‐treated group on Day 14 after ASD induction, whereas octamer‐binding transcription factor 4 (OCT4) expression was significantly decreased in the PPA‐treated group. The histological evaluation revealed significantly reduced granule cells diameter and granule cell layer (GCL) thickness in PPA‐treated rats compared with control rats. We suggest that PPA administration induced abnormal neural cell organization, which may have led to autism‐like neurobehaviors including increased in aggressive behavior, reduced in exploratory activity, and isolative and passive behaviors.Support or Funding InformationFunds: NRF‐2017R1A2A2A01067169, KGM4611714, 2016 Creative Research Program of Inje University, Republic of KoreaThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.