A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development

doi:10.18632/oncotarget.21381

CORC > 武汉物理与数学研究所 > 中国科学院武汉物理与数学研究所 > 磁共振应用研究部

	A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development
	Dong, Fengping 1; Shen, Yilun 1; Zou, Donghua 4; Deng, Dazhi 1,7; Wu, Yuan ; Zhang, Limin 2; Mao, Yingwei 1; Wang, Yonggang 3; Jian, Chongdong 1,6; Lei, Ling 1,5
刊名	ONCOTARGET
	2017-10-17
卷号	8 期号:49 页码:84798-84817
关键词	Disc1 Interneuron Neural Progenitors Metabolism Depression Pathology Section
DOI	10.18632/oncotarget.21381
文献子类	Article
英文摘要	Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 (DISC1), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation. Interestingly, prenatal interruption of mouse Disc1 function in NPCs leads to abnormal depression-like deficit in adult mice. Here we took a novel unbiased metabonomics approach to identify brain-specific metabolites that are significantly changed in DN-DISC1 mice. Surprisingly, the inhibitory neurotransmitter, GABA, is augmented. Consistently, parvalbumin (PV) interneurons are increased in the cingulate cortex, retrosplenial granular cortex, and motor cortex. Interestingly, somatostatin (SST) positive and neuropeptide Y (NPY) interneurons are decreased in some brain regions, suggesting that DN-DISC1 expression affects the localization of interneuron subtypes. To further explore the cellular mechanisms that cause this change, DN-DISC1 suppresses proliferation and promotes the cell cycle exit of progenitors in the medial ganglionic eminence (MGE), whereas it stimulates ectopic proliferation of neighboring cells through cell non-autonomous effect. Mechanistically, it modulates GSK3 activity and interrupts Dlx2 activity in the Wnt activation. In sum, our results provide evidence that specific genetic insults on NSCs at a short period of time could lead to prolonged changes of brain metabolism and development, eventually behavioral defects.
WOS关键词	CHILDHOOD-ONSET SCHIZOPHRENIA ; PARVALBUMIN-POSITIVE INTERNEURONS ; CORTICAL INTERNEURONS ; TRANSGENIC MICE ; MUTANT MICE ; GRAY-MATTER ; PROGENITOR PROLIFERATION ; HIPPOCAMPAL NEUROGENESIS ; SCOTTISH POPULATION ; AFFECTIVE-DISORDERS
WOS研究方向	Oncology ; Cell Biology
语种	英语
WOS记录号	WOS:000413077800029
资助机构	NARSAD ; NARSAD ; American Heart Association ; American Heart Association ; Guangxi Natural Science Foundation(2016GXNSFCA380012) ; Guangxi Natural Science Foundation(2016GXNSFCA380012) ; Natural Science Foundation of China(3127114 ; Natural Science Foundation of China(3127114 ; Shanghai Municipal Education Commission(20151414) ; Shanghai Municipal Education Commission(20151414) ; 31770800 ; 31770800 ; 81571329) ; 81571329) ; NARSAD ; NARSAD ; American Heart Association ; American Heart Association ; Guangxi Natural Science Foundation(2016GXNSFCA380012) ; Guangxi Natural Science Foundation(2016GXNSFCA380012) ; Natural Science Foundation of China(3127114 ; Natural Science Foundation of China(3127114 ; Shanghai Municipal Education Commission(20151414) ; Shanghai Municipal Education Commission(20151414) ; 31770800 ; 31770800 ; 81571329) ; 81571329)
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/11426]
专题	武汉物理与数学研究所_磁共振应用研究部
作者单位	1.Penn State Univ, Dept Biol, University Pk, PA 16802 USA 2.Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan, Hubei, Peoples R China 3.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Neurol, Shanghai, Peoples R China 4.First Peoples Hosp Nanning, Dept Neurol, Nanning, Peoples R China 5.Peoples Hosp Guangxi Zhuang Autonomous Reg, Hlth Examinat Ctr, Nanning, Peoples R China 6.Guangxi Med Univ, Affiliated Hosp 1, Dept Neurol, Nanning, Guangxi, Peoples R China 7.Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Emergency, Nanning, Peoples R China
推荐引用方式 GB/T 7714	Dong, Fengping,Shen, Yilun,Zou, Donghua,et al. A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development[J]. ONCOTARGET,2017,8(49):84798-84817.
APA	Dong, Fengping.,Shen, Yilun.,Zou, Donghua.,Deng, Dazhi.,Wu, Yuan.,...&McSweeney, Colleen.(2017).A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.ONCOTARGET,8(49),84798-84817.
MLA	Dong, Fengping,et al."A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development".ONCOTARGET 8.49(2017):84798-84817.