Sleep disturbances and the orexinergic system in a valproic acid model of autism

Abstract

Sleep disturbances are the most prevalent comorbidities in autistic individuals and have been implicated in the disorder’s aetiology, however, their exact role is not fully understood. This study aimed to evaluate the sex-specific effect of sleep on autism symptomology. Pregnant rats were given a single intraperitoneal injection of VPA, and their pups subjected to a 16hr dark/ 8hr light cycle to induce sleep disturbance. Autism-like features were assessed with marble burying, balance beam (BB), y-maze, novel object recognition (NOR) and three- chambered sociability behavioural tests. Three-way factorial ANOVAs were used to determine the interaction between sex, sleep and autism. Significance was found for the main effect for sleep condition in the time spent investigating the novel object (NOR) and the interaction between sex and sleep condition in the number of foot slips (BB). Additionally, a preliminary investigation of the cellular diversity of the lateral hypothalamic area (LHA) was provided to elucidate the orexinergic regulation of sleep/wake cycles. From descriptions of astrocytes, oligodendrocytes, and neurons, sleep condition was presumed to affect orexinergic signalling through the indirect excitation by nearby astrocyte populations. The results of the behavioural study support the growing understanding of a sex-specific presentation of autism and highlight the need for greater inclusivity in diagnostic criteria which are currently biased towards male presentations. Additionally, the results of the cytological investigation support the suggestion of hyperactive orexinergic functioning in autism and warrant research efforts into the underlying orexinergic control of sleep/wake functioning as a potential mechanism underlying its pathogenesis.