Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease

被引：85
|
作者：
Simpson, Jessica M. [2 ]
Gil-Mohapel, Joana [1 ,2 ]
Pouladi, Mahmoud A. [3 ,4 ,5 ]
Ghilan, Mohamed [2 ]
Xie, Yuanyun [3 ,4 ,5 ]
Hayden, Michael R. [3 ,4 ,5 ]
Christie, Brian R. [2 ,6 ,7 ,8 ]
机构：
[1] Univ Victoria, Div Med Sci, Isl Med Program, Victoria, BC V8W 2Y2, Canada
[2] Univ Victoria, Dept Biol, Victoria, BC V8W 2Y2, Canada
[3] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada
[4] Univ British Columbia, Ctr Mol Med & Therapeut, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada
[5] Univ British Columbia, Family Res Inst, Vancouver, BC V5Z 1M9, Canada
[6] Univ British Columbia, Brain Res Ctr, Vancouver, BC V5Z 1M9, Canada
[7] Univ British Columbia, Program Neurosci, Vancouver, BC V5Z 1M9, Canada
[8] Univ British Columbia, Dept Cellular & Physiol Sci, Vancouver, BC V5Z 1M9, Canada
来源：
NEUROBIOLOGY OF DISEASE | 2011年 / 41卷 / 02期
基金：
加拿大自然科学与工程研究理事会;
关键词：
Huntington disease; Adult neurogenesis; Cell proliferation; Dentate gyrus; Subventricular zone; YAC128 transgenic mice; Hippocampus; NEURONAL INTRANUCLEAR INCLUSIONS; CELL-PROLIFERATION; STEM-CELLS; INCREASES NEUROGENESIS; NEUROTROPHIC FACTOR; MUTANT HUNTINGTIN; GENE-EXPRESSION; DENTATE GYRUS; HEAT REPEATS; IN-VIVO;
D O I：
10.1016/j.nbd.2010.09.012
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Perturbations in neurogenesis in the adult brain have been implicated in impaired learning and memory. In the present study, we investigated which stages of the neurogenic process are affected in the transgenic YAC128 mouse model of Huntington disease (HD). Hippocampal neuronal proliferation was altered in the dentate gyrus (DG) of YAC128 mice as compared with wild-type (WT) littermate controls in early symptomatic to end-stage mice. In addition, we detected a significantly lower number of immature neurons in the DG of young, pre-symptomatic YAC128 mice. This decrease in neuronal differentiation persisted through the progression of the disease, and resulted in an overall reduction in the number of new mature neurons in the DG of YAC128 mice. There were no changes in cell proliferation and differentiation in the subventricular zone (SVZ). In this study, we demonstrate decreases in neurogenesis in the DG of YAC128 mice, and these deficits may contribute to the cognitive abnormalities observed in these animals. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.
引用
收藏
页码：249 / 260
页数：12
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