IDDRC, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
IDDRC, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Neurobiol Dis. 2022 Jan;162:105574. doi: 10.1016/j.nbd.2021.105574. Epub 2021 Nov 27.
Huntington's disease (HD) is a heritable, fatal neurodegenerative disorder caused by a mutation in the Huntingtin gene. It is characterized by chorea, as well as cognitive and psychiatric symptoms. Histopathologically, there is a massive loss of striatal projection neurons and less but significant loss in other areas throughout the cortico-basal ganglia-thalamocortical (CBGTC) loop. The mutant huntingtin protein has been implicated in numerous functions, including an important role in synaptic transmission. Most studies on anatomical and physiological alterations in HD have focused on striatum and cerebral cortex. However, based on recent CBGTC projectome evidence, the need to study other pathways has become increasingly clear. In this review, we examine the current status of our knowledge of morphological and electrophysiological alterations of those pathways in animal models of HD. Based on recent studies, there is accumulating evidence that synaptic disconnection, particularly along excitatory pathways, is pervasive and almost universal in HD, thus supporting a critical role of the huntingtin protein in synaptic transmission.
亨廷顿病（HD）是一种遗传性致命的神经退行性疾病，由亨廷顿基因的突变引起。它的特征是舞蹈症，以及认知和精神症状。组织病理学上，纹状体投射神经元大量丧失，而皮质基底节丘脑皮质（CBGTC）回路的其他区域虽然数量较少，但也有显著丧失。突变的亨廷顿蛋白与许多功能有关，包括在突触传递中发挥重要作用。大多数关于 HD 的解剖和生理改变的研究都集中在纹状体和大脑皮层。然而，基于最近的 CBGTC 项目组证据，研究其他途径的必要性变得越来越明显。在这篇综述中，我们检查了目前对 HD 动物模型中这些途径的形态和电生理改变的了解状况。基于最近的研究，有越来越多的证据表明，突触分离，特别是沿着兴奋性途径，在 HD 中普遍存在且几乎是普遍存在的，因此支持了亨廷顿蛋白在突触传递中的关键作用。
