title: Reduced expression of α5GABAAreceptors elicits autism-like alterations in EEG patterns and sleep-wake behavior.
abstract: A reduction in the activity of GABAAreceptors, particularly α5 subunit-containing GABAAreceptors (α5GABAARs), has been implicated in the etiology of Autism Spectrum Disorders (ASD). Genetically modified mice that lack α5GABAARs (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; 125mg/kg intraperitoneal injection) or vehicle and EEG and sleep-wake patterns were assessed. The results showed that Gabra5-/-mice (n=3) exhibited elevated 0-2Hz EEG activity during all sleep-wake states (all p<0.04), decreased 8-12Hz 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 α5GABAAR 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.
authors: Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Lia
authors: L
authors: Mesbah-Oskui
authors: Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors: Antonello
authors: A
authors: Penna
authors: Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Anesthesia, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada. Electronic address: beverley.orser@utoronto.ca.
authors: Beverley A
authors: BA
authors: Orser
authors: Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Electronic address: richard.horner@utoronto.ca.
authors: Richard L
authors: RL
authors: Horner
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012894:Sleep Stages / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014851:Wakefulness / Q000235:genetics / Q000502:physiology*
chemical_list: C496250:Gabra5 protein, mouse; D008070:Lipopolysaccharides; D011963:Receptors, GABA-A
keywords: Autism spectrum disorders; EEG; Extrasynaptic GABA(A) receptors; Inflammation; Sleep