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 wi...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 firstepisode treatment-naı¨ve 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.展开更多
To the Editor:Major depressive disorder(MDD)is a common mood disorder that contributes considerably to disability worldwide.Abnormalities in either structural connectivity or functional connectivity in the brains of p...To the Editor:Major depressive disorder(MDD)is a common mood disorder that contributes considerably to disability worldwide.Abnormalities in either structural connectivity or functional connectivity in the brains of patients with MDD have been widely reported,which greatly extends our knowledge of the pathophysiology of MDD.展开更多
基金supported by the National Natural Science Foundation of China(81630030,81130024,and 81528008)the National Natural Science Foundation of China/Research Grants Council of Hong Kong Joint Research Scheme(81461168029)+2 种基金the National Basic Research Development Program of China(2016YFC0904300)the Science and Technology Project of the Health Planning Committee of Sichuan(19PJ090)the National Natural Science Foundation of China for Distinguished Young Scholars(81501159).
文摘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 firstepisode treatment-naı¨ve 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.
基金Key Research and Development Program of Science and Technology Department of Sichuan Province(Nos.22ZDYF1531 and 22ZDYF1696)Program of Chengdu Science and Technology(No.2021-YF05-00272-SN)+3 种基金National Natural Science Foundation of China(No.82001432)China Postdoctoral Science Foundation(Nos.2020TQ0213 and 2020M683319)Open Project Program of the National Laboratory of Pattern Recognition(No.202000034)West China Hospital Postdoctoral Science Foundation(No.2020HXBH104)
文摘To the Editor:Major depressive disorder(MDD)is a common mood disorder that contributes considerably to disability worldwide.Abnormalities in either structural connectivity or functional connectivity in the brains of patients with MDD have been widely reported,which greatly extends our knowledge of the pathophysiology of MDD.
