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 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 rats were randomly divided into control and 500 mg/kg propionic acid (PPA)-treated groups. Rats were subjected to behavioral tests, gene expression analyses, and histological analyses to detect pathophysiological and neurobehavioral alterations. Exploratory activity and non-aggressive behavior were significantly reduced in PPA-treated rats, whereas enhanced aggressive behavior during adjacent interactions was observed on day 14 after PPA administration. To evaluate gene expression after PPA administration, we analyzed hippocampal tissue using reverse transcription PCR. Glial fibrillary acidic protein was augmented in the PPA-treated group on day 14 after appearance of ASD-like behaviors by PPA administration, whereas octamer-binding transcription factor 4 expression was significantly decreased in the PPA-treated group. Histological evaluation revealed significantly reduced diameter and layer thickness of granule cells in PPA-treated rats compared with control rats. We conclude that PPA administration induced abnormal neural cell organization, which may have led to autism-like neurobehaviors, including increased aggressive behavior, reduced exploratory activity, and isolative and passive behaviors.
Highlights
Autism spectrum disorder (ASD) is characterized by social deficits, repetitive and restricted behaviors, and alteration of brain development [1]
propionic acid (PPA)-treated rats did not show altered body weight compared with control rats during the early post-induction day (PID) period
The optimal PPA dose acts as a precursor for glucose production to make energy in ruminants and affects human physiological actions. Since some foods such as wheat and dairy products contain PPA as a preservative, such food intake may exacerbate the symptoms of ASD [20]
Summary
Autism spectrum disorder (ASD) is characterized by social deficits, repetitive and restricted behaviors, and alteration of brain development [1]. Several studies have reported an interrelation between brain development and autistic neurobehavior. Changes in hippocampal structures are related to ASD behavior [2]. Neurogenesis in the dentate gyrus is related to long-term potentiation in memory function [3] and the development of neuropsychiatric disorders [4] after birth. Approximately 15% of granule cells, which make up the dentate gyrus, are produced during embryogenesis [5]. The dentate gyrus is an important region involved in ASD development. Autism is usually diagnosed before 36 months of age. The disorder is highly heritable and neuropsychiatric, as evidenced by the higher concordance rates in monozygotic (82–92%) compared with dizygotic (1–10%) twins [7]. ASD is a neurodevelopmental disorder with a complex etiology that is not fully understood
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