Reduced expression of α5GABAA receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior

• Published in: Neurotoxicology and teratology 2017-05, Vol.61, p.115-122
• Main Authors: Mesbah-Oskui, Lia, M. Sc, Penna, Antonello, Ph.D., M.D, Orser, Beverley A., Ph.D., M.D, Horner, Richard L., Ph.D
• Format: Article
• Language: English
• Subjects: Autism spectrum disorders; EEG; Emergency; Extrasynaptic GABAA receptors; Inflammation; Medical Education; Sleep
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/j.ntt.2016.10.009

Abstract A reduction in the activity of GABAA receptors, particularly α5 subunit-containing GABAA receptors (α5GABAA Rs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABAA Rs ( Gabra5 − / − ) exhibit autism-like behaviors and both enhanced and impaired learning and memory, depending on the behavioral task. The aim of this study was to examine the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5 − / − mice and wild-type mice. In addition, since some individuals with ASD can exhibit elevated innate immune response, mice were treated with lipopolysaccharide (LPS; 125 mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed. The results showed that Gabra5 − / − mice ( n = 3) exhibited elevated 0 – 2 Hz EEG activity during all sleep-wake states (all p < 0.04), decreased 8 – 12 Hz EEG activity during REM sleep ( p = 0.04), and decreased sleep spindles under baseline conditions compared to wild-type controls ( n = 4) (all p ≤ 0.03). Alterations in EEG activity and sleep-wake behavior were identified in Gabra5 − / − mice following treatment with LPS, however these changes were similar to those in wild-type mice. Our findings support the hypothesis that reduced α5GABAA R activity contributes to an ASD phenotype. The results also suggest that Gabra5 − / − mice may serve as an animal model for ASD, as assessed through EEG activity and sleep-wake behaviors.