期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 427, 期 1, 页码 218-222出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.09.056
关键词
Alzheimer's disease; Dentate granule cells; Primary cilium; p75(NTR); Somatostatin receptor 3 (SSTR3); 3xTg-AD mice
资金
- Alzheimer Society of Canada (ASC) [09-14]
The hippocampal dentate gyrus is one of the two sites of continuous neurogenesis in adult rodents and humans. Virtually all dentate granule cells have a single immobile cilium with a microtubule spine or axoneme covered with a specialized cell membrane loaded with receptors such as the somatostatin receptor 3 (SSTR3), and the p75 neurotrophin receptor (p75(NTR)) The signals from these receptors have been reported to stimulate neuroprogenitor proliferation and the post-mitotic maturation of newborn granule cells into functioning granule cells. We have found that in 6-24-months-old triple transgenic Alzheimer's disease model mice (3xTg-AD) producing both A beta(1-42) and the mutant human tau protein tau(P301L), the dentate granule cells still had immunostainable SSTR3- and p75(NTR)-bearing cilia but they were only half the length of the immunostained cilia in the corresponding wild-type mice. However, the immunostainable length of the granule cell cilia was not reduced either in 2xTg-AD mice accumulating large amounts of A beta(1-42) or in mice accumulating only a mutant human tau protein. Thus it appears that a combination of A beta(1-42) and tau protein accumulation affects the levels of functionally important receptors in 3xTg-AD mice. These observations raise the important possibility that structural and functional changes in granule cell cilia might have a role in AD. Crown Copyright (C) 2012 Published by Elsevier Inc. All rights reserved.
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