کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021927 | 1580655 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of Alzheimer's disease
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کلمات کلیدی
PVDFNonidet-P40NP40MAP2PS1PFAAPPLRPpresenilin 1 - Presenilin 1long-term depression - افسردگی طولانی مدتAlzheimer's disease - بیماری آلزایمرlong-term potentiation - تقویت درازمدتLTP - تقویت طولانی مدت یا LTP dendritic spines - ستون دندریتیکCortex - قشرLTD - محدودTransgenic mice - موش ترانس ژنیکHippocampus - هیپوکامپ paraformaldehyde - پارافرمالدهیدMicrotubule associated protein 2 - پروتئین مرتبط با میکروتوبول 2Low-density lipoprotein receptor-related protein - پروتئین مرتبط با گیرنده های لیپوپروتئین کم چگالیamyloid precursor protein - پروتئین پیش ماده آمیلوئیPolyvinylidene fluoride - پلی وینیلیدین فلوراید
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of Alzheimer's disease RanBP9 overexpression accelerates loss of dendritic spines in a mouse model of Alzheimer's disease](/preview/png/6021927.png)
چکیده انگلیسی
We previously demonstrated that RanBP9 overexpression increased Aβ generation and amyloid plaque burden, subsequently leading to robust reductions in the levels of several synaptic proteins as well as deficits in the learning and memory skills in a mouse model of Alzheimer's disease (AD). In the present study, we found striking reduction of spinophilin-immunoreactive puncta (52%, p < 0.001) and spinophilin area (62.5%, p < 0.001) in the primary cortical neurons derived from RanBP9 transgenic mice (RanBP9-Tg) compared to wild-type (WT) neurons. Similar results were confirmed in WT cortical neurons transfected with EGFP-RanBP9. At 6-months of age, the total spine density in the cortex of RanBP9 single transgenic, APÎE9 double transgenic and APÎE9/RanBP9 triple transgenic mice was similar to WT mice. However, in the hippocampus the spine density was significantly reduced (27%, p < 0.05) in the triple transgenic mice compared to WT mice due to reduced number of thin spines (33%, p < 0.05) and mushroom spines (22%, p < 0.05). This suggests that RanBP9 overexpression in the APÎE9 mice accelerates loss of spines and that the hippocampus is more vulnerable. At 12-months of age, the cortex showed significant reductions in total spine density in the RanBP9 (22%, p < 0.05), APÎE9 (19%, p < 0.05) and APÎE9/RanBP9 (33%, p < 0.01) mice compared to WT controls due to reductions in mushroom and thin spines. Similarly, in the hippocampus the total spine density was reduced in the RanBP9 (23%, p < 0.05), APÎE9 (26%, p < 0.05) and APÎE9/RanBP9 (39%, p < 0.01) mice due to reductions in thin and mushroom spines. Most importantly, RanBP9 overexpression in the APÎE9 mice further exacerbated the reductions in spine density in both the cortex (14%, p < 0.05) and the hippocampus (16%, p < 0.05). Because dendritic spines are considered physical traces of memory, loss of spines due to RanBP9 provided the physical basis for the learning and memory deficits. Since RanBP9 protein levels are increased in AD brains, RanBP9 might play a crucial role in the loss of spines and synapses in AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 69, September 2014, Pages 169-179
Journal: Neurobiology of Disease - Volume 69, September 2014, Pages 169-179
نویسندگان
Ruizhi Wang, Juan Pablo Palavicini, Hongjie Wang, Panchanan Maiti, Elisabetta Bianchi, Shaohua Xu, B.N. Lloyd, Ken Dawson-Scully, David E. Kang, Madepalli K. Lakshmana,