Pérot Jean-Baptiste, Brouillet Emmanuel, Flament Julien
Laboratoire des Maladies Neurodégénératives, Molecular Imaging Research Center, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Paris-Saclay, Fontenay-aux-Roses, France.
Institut du Cerveau - Paris Brain Institute - ICM, Sorbonne Université, Paris, France.
Front Aging Neurosci. 2024 Feb 13;16:1306312. doi: 10.3389/fnagi.2024.1306312. eCollection 2024.
Huntington's disease is an inherited disorder characterized by psychiatric, cognitive, and motor symptoms due to degeneration of medium spiny neurons in the striatum. A prodromal phase precedes the onset, lasting decades. Current biomarkers include clinical score and striatal atrophy using Magnetic Resonance Imaging (MRI). These markers lack sensitivity for subtle cellular changes during the prodromal phase. MRI and MR spectroscopy offer different contrasts for assessing metabolic, microstructural, functional, or vascular alterations in the disease. They have been used in patients and mouse models. Mouse models can be of great interest to study a specific mechanism of the degenerative process, allow better understanding of the pathogenesis from the prodromal to the symptomatic phase, and to evaluate therapeutic efficacy. Mouse models can be divided into three different constructions: transgenic mice expressing exon-1 of human huntingtin (HTT), mice with an artificial chromosome expressing full-length human HTT, and knock-in mouse models with CAG expansion inserted in the murine htt gene. Several studies have used MRI/S to characterized these models. However, the multiplicity of modalities and mouse models available complicates the understanding of this rich corpus. The present review aims at giving an overview of results obtained using MRI/S for each mouse model of HD, to provide a useful resource for the conception of neuroimaging studies using mouse models of HD. Finally, despite difficulties in translating preclinical protocols to clinical applications, many biomarkers identified in preclinical models have already been evaluated in patients. This review also aims to cover this aspect to demonstrate the importance of MRI/S for studying HD.
亨廷顿舞蹈症是一种遗传性疾病，其特征为精神、认知和运动症状，这是由于纹状体中中等棘状神经元退化所致。在发病前有一个前驱期，持续数十年。目前的生物标志物包括临床评分以及使用磁共振成像（MRI）检测的纹状体萎缩情况。这些标志物在前驱期对细微的细胞变化缺乏敏感性。MRI和磁共振波谱提供了不同的对比度，用于评估该疾病中的代谢、微观结构、功能或血管改变。它们已被应用于患者和小鼠模型。小鼠模型对于研究退行性过程的特定机制可能非常有意义，有助于更好地理解从前驱期到症状期的发病机制，并评估治疗效果。小鼠模型可分为三种不同的构建类型：表达人亨廷顿蛋白（HTT）外显子1的转基因小鼠、携带表达全长人HTT的人工染色体的小鼠，以及在小鼠htt基因中插入CAG扩增的敲入小鼠模型。多项研究已使用MRI/S对这些模型进行表征。然而，可用的模态和小鼠模型种类繁多，使得理解这一丰富的研究内容变得复杂。本综述旨在概述使用MRI/S对每种HD小鼠模型所获得的结果，为使用HD小鼠模型进行神经影像学研究的构思提供有用的资源。最后，尽管将临床前方案转化为临床应用存在困难，但在临床前模型中鉴定出的许多生物标志物已在患者中进行了评估。本综述还旨在涵盖这一方面，以证明MRI/S对研究HD的重要性。
