Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California-Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA.
ASN Neuro. 2010 Apr 7;2(2):e00033. doi: 10.1042/AN20090058.
The discovery of the HD (Huntington's disease) gene in 1993 led to the creation of genetic mouse models of the disease and opened the doors for mechanistic studies. In particular, the early changes and progression of the disease could be followed and examined systematically. The present review focuses on the contribution of these genetic mouse models to the understanding of functional changes in neurons as the HD phenotype progresses, and concentrates on two brain areas: the striatum, the site of most conspicuous pathology in HD, and the cortex, a site that is becoming increasingly important in understanding the widespread behavioural abnormalities. Mounting evidence points to synaptic abnormalities in communication between the cortex and striatum and cell-cell interactions as major determinants of HD symptoms, even in the absence of severe neuronal degeneration and death.
1993 年，HD（亨廷顿病）基因的发现导致了该疾病的遗传小鼠模型的创建，并为机制研究开辟了道路。特别是，可以系统地跟踪和检查疾病的早期变化和进展。本综述重点介绍了这些遗传小鼠模型对理解 HD 表型进展过程中神经元功能变化的贡献，并集中于两个脑区：纹状体，HD 最明显的病理学部位，以及皮层，皮层在理解广泛的行为异常方面变得越来越重要。越来越多的证据表明，皮层与纹状体之间的突触异常以及细胞间相互作用是 HD 症状的主要决定因素，即使在没有严重神经元变性和死亡的情况下也是如此。
