Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron-astrocyte-microglia dysregulation

Translational Psychiatry
Rigil K YeungHong Xue

Abstract

Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure. In addition, the KO mice were highly susceptible to audiogenic epilepsy. Some of the behavioral phenotypes showed evidence of imprinting, gender effect and amelioration by the antipsychotic risperidone, and the audiogenic epilepsy was inhibited by the antiepileptic diazepam. GABAergic parvalbumin (PV)-positive interneuron dystrophy, astrocyte dystrophy, and extensive microglia activation were observed in the frontotemporal corticolimbic regions, and reducti...Continue Reading

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Citations

Jan 22, 2019·Current Opinion in Neurology·Snezana MaljevicHolger Lerche
Aug 15, 2020·Human Molecular Genetics·George Andrew S InglisAndrew Escayg
Feb 2, 2019·European Archives of Psychiatry and Clinical Neuroscience·Qingqing ZhangYili Wu

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Methods Mentioned

BETA
ELISA
MDA
PCR
sedation
g

Software Mentioned

Prism
Graph Pad

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