A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development
文献类型：期刊论文
| 作者 | Wu, Yuan; Zhang, Limin6; Mao, Yingwei7; Deng, Dazhi1,7; Jian, Chongdong2,7; Lei, Ling3,7; McSweeney, Colleen7; Zhou, Yijing7; Dong, Fengping7; Shen, Yilun7 |
| 刊名 | ONCOTARGET
 |
| 出版日期 | 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) |
| 源URL | [http://ir.wipm.ac.cn/handle/112942/11434]  |
| 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.Peoples Hosp Guangxi Zhuang Autonomous Reg, Dept Emergency, Nanning, Peoples R China 2.Guangxi Med Univ, Affiliated Hosp 1, Dept Neurol, Nanning, Guangxi, Peoples R China 3.Peoples Hosp Guangxi Zhuang Autonomous Reg, Hlth Examinat Ctr, Nanning, Peoples R China 4.First Peoples Hosp Nanning, Dept Neurol, Nanning, Peoples R China 5.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Neurol, Shanghai, Peoples R China 6.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 7.Penn State Univ, Dept Biol, University Pk, PA 16802 USA |
| 推荐引用方式 GB/T 7714 | Wu, Yuan,Zhang, Limin,Mao, Yingwei,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 | Wu, Yuan.,Zhang, Limin.,Mao, Yingwei.,Deng, Dazhi.,Jian, Chongdong.,...&Wang, Yonggang.(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 | Wu, Yuan,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. |
入库方式： OAI收割
来源：武汉物理与数学研究所
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