Reduced expression of alpha 5GABA(A) receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior
A reduction in the activity of GABAA receptors, particularly ot5 subunit-containing GABAA receptors (alpha 5GABA(A)Rs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack alpha 5GABA(A)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 :5 0.03). Alterations in EEG activity and sleep-wake behavior were identified in Gabra5-1- mice following treatment with LPS, however these changes were similar to those in wild-type mice. Our findings support the hypothesis that reduced Gabra5(-/-) 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. (C) 2016 The Authors. Published by Elsevier Inc.
|Título según WOS:||ID WOS:000403512700013 Not found in local WOS DB|
|Título de la Revista:||NEUROTOXICOLOGY AND TERATOLOGY|
|Editorial:||PERGAMON-ELSEVIER SCIENCE LTD|
|Fecha de publicación:||2017|
|Página de inicio:||115|