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

Chengcheng Zhang, Peiyan Ni, Yikang Liu, Yang Tian, Jinxue Wei, Bo Xiang, Liansheng Zhao, Xiaojing Li, Xiaohong Ma, Wei Deng, Wanjun Guo, Rongjun Ni, Yamin Zhang, Qiang Wang, Hailiang Huang, Nanyin Zhang, Tao Li

Research output: Contribution to journalArticle

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 found significantly decreased gray and white matter in sensorimotor cortico-striatal networks in schizophrenic patients. The psychiatric risk alleles of the GABA pathway also displayed a significant negative correlation with the GMVs of the somatosensory cortex in patients. Our study identified that ErbB4 ablation in parvalbumin interneurons induced GABAergic dysregulation, providing valuable mechanistic insights into the sensorimotor cortico-striatal community structure deficits associated with schizophrenia.

Original languageEnglish (US)
JournalNeuroscience Bulletin
DOIs
StateAccepted/In press - Jan 1 2019

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Corpus Striatum
Knockout Mice
Schizophrenia
gamma-Aminobutyric Acid
Parvalbumins
Diffusion Magnetic Resonance Imaging
Somatosensory Cortex
Interneurons
Alleles
Sensory Gating
Brain
Therapeutics
Cerebral Cortex
Psychiatry
Real-Time Polymerase Chain Reaction
Magnetic Resonance Imaging
Messenger RNA
Gray Matter
Genes
Prepulse Inhibition

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Zhang, Chengcheng ; Ni, Peiyan ; Liu, Yikang ; Tian, Yang ; Wei, Jinxue ; Xiang, Bo ; Zhao, Liansheng ; Li, Xiaojing ; Ma, Xiaohong ; Deng, Wei ; Guo, Wanjun ; Ni, Rongjun ; Zhang, Yamin ; Wang, Qiang ; Huang, Hailiang ; Zhang, Nanyin ; Li, Tao. / GABAergic Abnormalities Associated with Sensorimotor Cortico-striatal Community Structural Deficits in ErbB4 Knockout Mice and First-Episode Treatment-Naïve Patients with Schizophrenia. In: Neuroscience Bulletin. 2019.
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GABAergic Abnormalities Associated with Sensorimotor Cortico-striatal Community Structural Deficits in ErbB4 Knockout Mice and First-Episode Treatment-Naïve Patients with Schizophrenia. / Zhang, Chengcheng; Ni, Peiyan; Liu, Yikang; Tian, Yang; Wei, Jinxue; Xiang, Bo; Zhao, Liansheng; Li, Xiaojing; Ma, Xiaohong; Deng, Wei; Guo, Wanjun; Ni, Rongjun; Zhang, Yamin; Wang, Qiang; Huang, Hailiang; Zhang, Nanyin; Li, Tao.

In: Neuroscience Bulletin, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Tian, Yang

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AU - Xiang, Bo

AU - Zhao, Liansheng

AU - Li, Xiaojing

AU - Ma, Xiaohong

AU - Deng, Wei

AU - Guo, Wanjun

AU - Ni, Rongjun

AU - Zhang, Yamin

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