کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
11031668 | 1645941 | 2018 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sleep and circadian abnormalities precede cognitive deficits in R521C FUS knockin rats
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 72, December 2018, Pages 159-170
Journal: Neurobiology of Aging - Volume 72, December 2018, Pages 159-170
نویسندگان
Tao Zhang, Xin Jiang, Min Xu, Haifang Wang, Xiao Sang, Meiling Qin, Puhua Bao, Ruiqi Wang, Chenchen Zhang, Huiping Lu, Yuzhuo Li, Jin Ren, Hung-Chun Chang, Jun Yan, Qiang Sun, Jin Xu,