GABAergic Abnormalities Associated with Sensorimotor Cortico-striatal Community Structural Deficits in ErbB4 Knockout Mice and First-Episode Treatment-Naïve Patients with Schizophrenia.

Neuroscience Bulletin
Chengcheng ZhangTao Li

Abstract

The current study was designed to explore how disruption of specific molecular circuits in the cerebral cortex may cause sensorimotor cortico-striatal community structure deficits in both a mouse model and patients with schizophrenia. We used prepulse inhibition (PPI) and brain structural and diffusion MRI scans in 23 mice with conditional ErbB4 knockout in parvalbumin interneurons and 27 matched controls. Quantitative real-time PCR was used to assess the differential levels of GABA-related transcripts in brain regions. Concurrently, we measured structural and diffusion MRI and the cumulative contribution of risk alleles in the GABA pathway genes in first-episode treatment-naïve schizophrenic patients (n = 117) and in age- and sex-matched healthy controls (n = 86). We present the first evidence of gray and white matter impairment of right sensorimotor cortico-striatal networks and reproduced the sensorimotor gating deficit in a mouse model of schizophrenia. Significant correlations between gray matter volumes (GMVs) in the somatosensory cortex and PPI as well as glutamate decarboxylase 1 mRNA expression were found in controls but not in knockout mice. Furthermore, these findings were confirmed in a human sample in which we foun...Continue Reading

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Methods Mentioned

BETA
transgenic
MDS
PCA

Software Mentioned

MatLab
PRSice
DARTEL SPM8
SPSS
GeneMANIA
FMRIB
FMRIB Diffusion Toolbox

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