Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, 18 Innovation Walk, Clayton, VIC, 3800, Australia.
Department of Neurology, Stem Cell Program & Institute for Regenerative Cures, University of California Davis Health Systems, 2921 Stockton Blvd, Sacramento, CA, 95817, USA.
Neurosci Biobehav Rev. 2019 Mar;98:194-207. doi: 10.1016/j.neubiorev.2019.01.015. Epub 2019 Jan 15.
To improve the translational predictability of treatment strategies for Huntington's disease (HD), sensitive and analogous cognitive outcomes are needed across HD animal models and humans. Spatial memory measures are promising candidates because they are based on 'visual' or 'non-verbal' cognition, and are commonly tested in both animals and humans. Here, we consider the suitability of spatial memory for strengthening translational links between animals and humans in HD research and clinical trials. We describe findings of spatial memory impairments in human HD and mouse models, including which aspects of spatial memory are most affected and at which time points in disease progression. We also describe the neural systems that underlie spatial memory and link spatial memory impairments to HD neuropathology, focussing on striatal and hippocampal systems. We provide a critical analysis of the literature in terms of the suitability of spatial memory for bridging the translational gap between species. Finally, we discuss possible neural mechanisms that might explain the spatial memory impairments seen in HD, and their relevance to potential treatments.
为了提高亨廷顿病 (HD) 治疗策略的转化预测能力，需要在 HD 动物模型和人类中具有敏感和类似的认知结果。空间记忆测量是有前途的候选方法，因为它们基于“视觉”或“非言语”认知，并且在动物和人类中通常都进行测试。在这里，我们考虑了空间记忆在加强 HD 研究和临床试验中动物与人类之间转化联系的适用性。我们描述了人类 HD 和小鼠模型中空间记忆受损的发现，包括空间记忆的哪些方面受到的影响最大，以及在疾病进展的哪个时间点受到的影响最大。我们还描述了空间记忆的神经基础，并将空间记忆损伤与 HD 神经病理学联系起来，重点关注纹状体和海马系统。我们根据空间记忆在跨越物种的转化差距方面的适用性，对文献进行了批判性分析。最后，我们讨论了可能解释 HD 中观察到的空间记忆损伤的神经机制，以及它们与潜在治疗方法的相关性。
