Autism spectrum disorder (ASD): zinc suppresses cerebellar ultrastructural alterations and modulates the oxidative stress/gliosis/neuronal loss axis-mediated ASD.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that typically appears in early childhood, and there is a link between ASD and zinc deficiency. Neither the potential protective effects of the trace element zinc on the cerebellum against ultrastructural damage in animal models of ASD, nor its ability to protect against the modulation of the oxidative stress/gliosis/neuronal loss axis implicated in autism, have been previously investigated. Young rats were injected with the short-chain fatty acid produced by gut bacteria that is known to induce ASD, propionic acid (PPA) (500 mg/kg) for 5 days (model group) and the protection group was treated with 2 mg/kg zinc sulfate for two weeks following PPA injections. Cerebellum damage and behavioral impairment developed in the model group of rats as demonstrated by profound cerebellar ultrastructural alterations such as degeneration of Purkinje neurons and fragmented endoplasmic reticulum, as well as anxiety-like behavior and social interaction deficits. PPA also significantly (p < .05) modulated the cerebellar protein levels of the gliosis biomarker GFAP and the neuronal loss biomarker calbindin D28K, as well as the cerebellar tissue levels of zinc, glutathione, and the oxidative stress biomarker malondialdehyde (MDA). All these parameters were significantly (p < .05) protected by zinc treatment. Additionally, we observed a significant (p < .001) correlation between the degree of Purkinje cell damage and these parameters associated with autism. In conclusion, PPA-induced autistic behaviors in rats are associated with alteration to the cerebellar ultrastructure, modulation of the oxidative stress/gliosis/neuronal loss axis of ASD, and a decline in zinc and glutathione, which were protected by zinc treatment.