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在非人类灵长类动物中模拟与脑部疾病相关的行为:我们做到了吗?

Modelling behaviors relevant to brain disorders in the nonhuman primate: Are we there yet?

作者信息

Scott Jack T, Bourne James A

机构信息

Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.

Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, Australia.

出版信息

Prog Neurobiol. 2022 Jan;208:102183. doi: 10.1016/j.pneurobio.2021.102183. Epub 2021 Oct 30.

Abstract

Recent years have seen a profound resurgence of activity with nonhuman primates (NHPs) to model human brain disorders. From marmosets to macaques, the study of NHP species offers a unique window into the function of primate-specific neural circuits that are impossible to examine in other models. Examining how these circuits manifest into the complex behaviors of primates, such as advanced cognitive and social functions, has provided enormous insights to date into the mechanisms underlying symptoms of numerous neurological and neuropsychiatric illnesses. With the recent optimization of modern techniques to manipulate and measure neural activity in vivo, such as optogenetics and calcium imaging, NHP research is more well-equipped than ever to probe the neural mechanisms underlying pathological behavior. However, methods for behavioral experimentation and analysis in NHPs have noticeably failed to keep pace with these advances. As behavior ultimately lies at the junction between preclinical findings and its translation to clinical outcomes for brain disorders, approaches to improve the integrity, reproducibility, and translatability of behavioral experiments in NHPs requires critical evaluation. In this review, we provide a unifying account of existing brain disorder models using NHPs, and provide insights into the present and emerging contributions of behavioral studies to the field.

摘要

近年来,使用非人类灵长类动物(NHPs)来模拟人类脑部疾病的研究活动有了显著复兴。从狨猴到猕猴,对非人类灵长类物种的研究为了解灵长类特有的神经回路功能提供了一个独特的窗口,而这些功能在其他模型中是无法研究的。研究这些神经回路如何表现为灵长类动物的复杂行为,如高级认知和社交功能,到目前为止已经为众多神经和神经精神疾病症状的潜在机制提供了大量见解。随着现代体内操纵和测量神经活动技术(如光遗传学和钙成像)的不断优化,非人类灵长类动物研究比以往任何时候都更有能力探究病理行为背后的神经机制。然而,非人类灵长类动物行为实验和分析方法明显未能跟上这些进展。由于行为最终处于临床前研究结果与其转化为脑部疾病临床结果的交汇点,因此改进非人类灵长类动物行为实验的完整性、可重复性和可转化性的方法需要进行批判性评估。在这篇综述中,我们对现有的使用非人类灵长类动物的脑部疾病模型进行了统一阐述,并深入探讨了行为研究对该领域目前及未来的贡献。

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