EARLY ACTIVATION OF MICROGLIA AND ASTROCYTES IN MOUSE MODELS OF SPINOCEREBELLAR ATAXIA TYPE 1

被引：84
作者：
Cvetanovic, M. [1 ]
Ingram, M. [2 ]
Orr, H. [2 ]
Opal, P. [3 ,4 ]
机构：
[1] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[3] Northwestern Univ, Chicago, IL 60611 USA
[4] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA
来源：
NEUROSCIENCE | 2015年 / 289卷
基金：
美国国家卫生研究院;
关键词：
spinocerebellar ataxia type 1; SCA1; neurodegeneration; glia; astrocytes; microglia; MUTANT HUNTINGTIN; TRANSGENIC MICE; SYNAPSE FORMATION; DISEASE; SCA1; INFLAMMATION; EXPRESSION; NEURONS; SYSTEM; GLIA;
D O I：
10.1016/j.neuroscience.2015.01.003
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Spinocerebellar ataxia type 1 (SCA1) is an incurable, dominantly inherited neurodegenerative disease of the cerebellum caused by a polyglutamine-repeat expansion in the protein ataxin-1 (ATXN1). While analysis of human autopsy material indicates significant glial pathology in SCA1, previous research has focused on characterizing neuronal dysfunction. In this study, we characterized astrocytic and microglial response in SCA1 using a comprehensive array of mouse models. We have discovered that astrocytes and microglia are activated very early in SCA1 pathogenesis even when mutant ATXN1 expression was limited to Purkinje neurons. Glial activation occurred in the absence of neuronal death, suggesting that glial activation results from signals emanating from dysfunctional neurons. Finally, in all different models examined glial activation closely correlated with disease progression, supporting the development of glial-based biomarkers to follow disease progression. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：289 / 299
页数：11
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