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

Abstract:

:A reduction in the activity of GABAA receptors, particularly α5 subunit-containing GABAA receptors (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.

journal_name

Neurotoxicol Teratol

authors

Mesbah-Oskui L,Penna A,Orser BA,Horner RL

doi

10.1016/j.ntt.2016.10.009

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

115-122

eissn

0892-0362

issn

1872-9738

pii

S0892-0362(16)30121-0

journal_volume

61

pub_type

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