Etiology of Sleep Disorders in ASD (Autism Spectrum Disorders): Role for Inflammatory Cytokines

Abstract

Abstract : Sleep disruptions are a common clinical feature observed in children with autism spectrum disorders (ASD). These include irregular sleep-wake patterns, delayed sleep latencies, and problems with sleep maintenance. The etiology of these sleep disturbances is unknown and remains relatively unexplored in any animal model of ASD. Prenatal valproic acid (VPA) exposure is a proposed model of ASD. Pups exposed to VPA in utero show similar characteristics to children with ASD, including abnormalities in brain morphology and sex-specific behavioral deficits. With this model, we examined the sleep architecture of prenatally, VPA- treated juvenile rats (PN31-34). We used a telemetry system to record electroencephalogram and electromyogram activity of each animal. Two 12-hour light phases (PN 31 and PN 34) were manually scored for each vigilance state and the data were averaged for each animal. VPA-treated animals showed a change in sleep patterning, with more consolidated bouts of wake (60.1% increase in average bout length; t(11)=5.783, p=0.0001) and non-REM sleep (21.8% increase; t(11)=4.066, p=0.0019) as well as fewer transitions into wake and non-REM sleep. There was a significant decrease in the number of transitions from wake to non-REM sleep (36%; t(11)=8.657, p<0.0001), non-REM sleep to wake (30.7%; t(11)=6.974, p<0.0001), and REM sleep to wake (52.8%; t(11)=5.712, p=0.0001). Total sleep time and delta power, however, were similar in VPA-treated and controls animals. While these disruptions did not alter the total amount of acquired sleep in the animal?s sleep phase, the alterations in patterning may disrupt sleep-dependent functions such as metabolic homeostasis, maintenance of the stress axis and synaptic plasticity. To our knowledge this is the first report of an ASD animal model mimicking clinical sleep disruption.