Deletion of Schizophrenia Susceptibility Gene Ulk4 Leads to Abnormal Cognitive Behaviors via Akt-GSK-3 Signaling Pathway in Mice
文献类型：期刊论文
| 作者 | Hu, Ling2,3,4; Zhou, Bing-Yao3,4; Yang, Cui-Ping5,6; Lu, Da-Yun1; Tao, Yun-Chao3,4; Chen, Lin5,6; Zhang, Lei5,6; Su, Jun-Hui5,6; Huang, Ying2; Song, Ning-Ning2,3,4 |
| 刊名 | SCHIZOPHRENIA BULLETIN
 |
| 出版日期 | 2022-05-06 |
| 页码 | 10 |
| ISSN号 | 0586-7614 |
| 关键词 | Unc-51-like kinase 4 schizophrenia sensorimotor gating Akt GSK-3 cerebral cortex |
| DOI | 10.1093/schbul/sbac040 |
| 通讯作者 | Ding, Yu-Qiang(dingyuqiang@vip.163.com) |
| 英文摘要 | Objectives Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing. Methods We generated Emx1-Cre:Ulk4(flox/flox) conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus. Results The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3 alpha/beta were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1 alpha (PP1 alpha). Indeed, the reduction of p-Akt and p-GSK-3 alpha/beta was rescued by administration of inhibitor acting on PP2A and PP1 alpha in CKO mice. Conclusions Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice. |
| WOS关键词 | CORTICAL PYRAMIDAL NEURONS ; DENDRITIC SPINE DENSITY ; CORTEX ; GSK-3 ; INHIBITION ; EXPRESSION ; SATB2 ; CELLS |
| 资助项目 | National Natural Science Foundation of China[31771134] ; National Natural Science Foundation of China[31671061] ; National Natural Science Foundation of China[82071507] ; National Natural Science Foundation of China[81571332] ; National Natural Science Foundation of China[91232724] ; Shanghai Pujiang Program[20PJ1413300] ; Key Research and Development Program from Hunan Province[2018DK2011] ; Collaborative Innovation Program of Shanghai Municipal Health Commission[2020CXJQ01] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX01] ; Zhangjiang (ZJ) Lab, and Shanghai Center for Brain Science and Brain-Inspired Technology |
| WOS研究方向 | Psychiatry |
| 语种 | 英语 |
| 出版者 | OXFORD UNIV PRESS |
| WOS记录号 | WOS:000791491800001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299370]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ding, Yu-Qiang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai, Peoples R China 2.Fudan Univ, Dept Lab Anim Sci, Shanghai 200032, Peoples R China 3.Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai 200032, Peoples R China 4.Fudan Univ, MOE Frontiers Ctr Brain Sci, Inst Brain Sci, Shanghai 200032, Peoples R China 5.Tongji Univ, East Hosp, Minist Educ, Key Lab Arrhythmias,Sch Med, Shanghai 200032, Peoples R China 6.Tongji Univ, Dept Anat & Neurobiol, Sch Med, Shanghai 200032, Peoples R China 7.Cent South Univ, Xiangya Hosp 2, Natl Clin Res Ctr Mental Hlth, Dept Psychiat, Changsha, Hunan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Ling,Zhou, Bing-Yao,Yang, Cui-Ping,et al. Deletion of Schizophrenia Susceptibility Gene Ulk4 Leads to Abnormal Cognitive Behaviors via Akt-GSK-3 Signaling Pathway in Mice[J]. SCHIZOPHRENIA BULLETIN,2022:10. |
| APA | Hu, Ling.,Zhou, Bing-Yao.,Yang, Cui-Ping.,Lu, Da-Yun.,Tao, Yun-Chao.,...&Ding, Yu-Qiang.(2022).Deletion of Schizophrenia Susceptibility Gene Ulk4 Leads to Abnormal Cognitive Behaviors via Akt-GSK-3 Signaling Pathway in Mice.SCHIZOPHRENIA BULLETIN,10. |
| MLA | Hu, Ling,et al."Deletion of Schizophrenia Susceptibility Gene Ulk4 Leads to Abnormal Cognitive Behaviors via Akt-GSK-3 Signaling Pathway in Mice".SCHIZOPHRENIA BULLETIN (2022):10. |
入库方式： OAI收割
来源：上海药物研究所
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