Abstract
The implication of different dietary n-3/n-6 polyunsaturated fatty acids (PUFAs) ratios has been investigated in some neurodevelopmental disorders (including autism and depression). However, the mechanisms underlying the effects of different PUFAs ratios on the autism are still poorly understood. In the present study, a valproic acid (VPA) rat model of autism was used to study the effects of diet with different n-3/n-6 PUFA ratios on the autism, and the underlying mechanisms explored. Our results showed that rats with prenatal administration of VPA took less response time to sniff three odorants in the olfactory habituation/dishabituation tests, had lower frequency of pinning and following patterns, and had decreased hippocampal 5-hydroxytryptamine (5-HT), increased serum 5-HT and downregulated expression of tight junction protein (occludin and claudin-1) in the colon. However, supplementation of n-3/n-6 PUFAs (1:5) in the VPA treated rats ameliorated the autistic behaviors, increased hippocampal 5-HT and tight junction expression in the colon, and decreased serum 5-HT. In conclusion, dietary supplementation of n-3/n-6 PUFAs (1:5) significantly improves VPA-induced autism-like behaviors in rats, which may be, at least partially, related to the increased hippocampal 5-HT. Furthermore, this diet can increase the expression of tight junction proteins to improve intestinal barrier impairment.
Highlights
The autism spectrum disorder (ASD), a type of developmental neurobiological disorders, is characterized by the pervasive impairments of social interaction and communication capabilities, and the restricted, repetitive, and stereotyped behaviors, activities, and interests [1]
Prenatal administration of valproic acid (VPA) (Pre-VPA) in rats is an acceptable practice in the establishment of animal model of autism, and these autistic rodents have a wide range of characteristics similar to those in humans [6]
In vitro studies have indicated that 5‐HT affects tight junction expression in Caco‐ 2 intestinal epithelial cells [23]. 5-HT is involved in the modulation of hypotonicity-induced increase of duodenal mucosal permeability [24]
Summary
The autism spectrum disorder (ASD), a type of developmental neurobiological disorders, is characterized by the pervasive impairments of social interaction and communication capabilities, and the restricted, repetitive, and stereotyped behaviors, activities, and interests [1]. Valproic acid (VPA) is used as an anticonvulsant and mood-stabilizing drug, and there is evidence showing that prenatal VPA exposure may cause maladaptive behaviors and birth defects and increase the risk of autism [4]. Results showed rats treated with VPA at embryo day 12.5 (E12.5) developed ASD syndromes. Prenatal administration of VPA (Pre-VPA) in rats is an acceptable practice in the establishment of animal model of autism, and these autistic rodents have a wide range of characteristics similar to those in humans [6]
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