Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats
文献类型：期刊论文
| 作者 | Zhang, Tao1,3; Jiang, Xin1,3; Xu, Min3; Wang, Haifang3; Sang, Xiao3; Qin, Meiling3; Bao, Puhua3; Wang, Ruiqi3; Zhang, Chenchen3; Lu, Huiping3 |
| 刊名 | NEUROBIOLOGY OF AGING
 |
| 出版日期 | 2018-12 |
| 卷号 | 72页码:159-170 |
| ISSN号 | 0197-4580 |
| 关键词 | FUS ALS FTD Cognitive impairment Sleep-wake cycle Circadian rhythm |
| DOI | 10.1016/j.neurobiolaging.2018.08.025 |
| 文献子类 | Article |
| 英文摘要 | Mutations in fused in sarcoma (Fus) cause familial amyotrophic lateral sclerosis (ALS) and occasionally frontotemporal dementia. Here we report the establishment and characterization of a novel knockin (KI) rat model expressing a Fus point mutation (R521C) via CRISPR/Cas9. The mutant animals developed adult-onset learning and memory behavioral deficits, with reduced spine density in hippocampal neurons. Remarkably, sleep-wake cycle and circadian abnormalities preceded the onset of cognitive deficit. RNA-seq study further demonstrated altered expression of some key sleep and circadian regulators, such as orexin/hypocretin receptor type 2 and casein kinase 1 epsilon, in the mutant rats. Therefore, we have established a rodent model expressing physiological level of a pathogenic mutant FUS, and we found cognitive impairment as a main behavioral deficit at mid age. Furthermore, we have revealed a new role of FUS in sleep and circadian regulation and demonstrated that functional change in FUS could cause sleep-wake and circadian disturbance as early symptoms. (C) 2018 Elsevier Inc. All rights reserved. |
| WOS关键词 | AMYOTROPHIC-LATERAL-SCLEROSIS ; RNA-BINDING PROTEIN ; FRONTOTEMPORAL LOBAR DEGENERATION ; MOTOR-NEURON DEGENERATION ; LARGE GENE LISTS ; SARCOMA FUS ; DENDRITIC SPINES ; POLYMERASE-II ; DNA-DAMAGE ; CLOCK |
| 资助项目 | National Natural Science Foundation of China[81771425] ; National Natural Science Foundation of China[31571209] ; Chinese Ministry of Science and Technology[2015ZX09102005002] ; Chinese Academy of Sciences[XDB02060006] ; Natural Science Foundation of Shanghai[16ZR1448800] |
| WOS研究方向 | Geriatrics & Gerontology ; Neurosciences & Neurology |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCIENCE INC |
| WOS记录号 | WOS:000449073700016 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279487]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Sun, Qiang; Xu, Jin |
| 作者单位 | 1.Univ Chinese Acad Sci, Shanghai, Peoples R China; 2.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, State Key Lab New Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Tao,Jiang, Xin,Xu, Min,et al. Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats[J]. NEUROBIOLOGY OF AGING,2018,72:159-170. |
| APA | Zhang, Tao.,Jiang, Xin.,Xu, Min.,Wang, Haifang.,Sang, Xiao.,...&Xu, Jin.(2018).Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats.NEUROBIOLOGY OF AGING,72,159-170. |
| MLA | Zhang, Tao,et al."Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats".NEUROBIOLOGY OF AGING 72(2018):159-170. |
入库方式： OAI收割
来源：上海药物研究所
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