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改善衰老相关疾病认知功能从临床前到临床的转化:普通狨猴中综合触摸屏测试组合的效用

Improving preclinical to clinical translation of cognitive function for aging-related disorders: the utility of comprehensive touchscreen testing batteries in common marmosets.

作者信息

Murai Takeshi, Bailey Lauren, Schultz Laura, Mongeau Lauren, DeSana Andrew, Silva Afonso C, Roberts Angela C, Sukoff Rizzo Stacey J

机构信息

Aging Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Department of Neurobiology, University of Pittsburgh School of Medicine, 514A Bridgeside Point 1, 100 Technology Drive, Pittsburgh, PA, 15219, USA.

出版信息

Cogn Affect Behav Neurosci. 2024 Apr;24(2):325-348. doi: 10.3758/s13415-023-01144-x. Epub 2024 Jan 10.

Abstract

Concerns about poor animal to human translation have come increasingly to the fore, in particular with regards to cognitive improvements in rodent models, which have failed to translate to meaningful clinical benefit in humans. This problem has been widely acknowledged, most recently in the field of Alzheimer's disease, although this issue pervades the spectrum of central nervous system (CNS) disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Consequently, recent efforts have focused on improving preclinical to clinical translation by incorporating more clinically analogous outcome measures of cognition, such as touchscreen-based assays, which can be employed across species, and have great potential to minimize the translational gap. For aging-related research, it also is important to incorporate model systems that facilitate the study of the long prodromal phase in which cognitive decline begins to emerge and which is a major limitation of short-lived species, such as laboratory rodents. We posit that to improve translation of cognitive function and dysfunction, nonhuman primate models, which have conserved anatomical and functional organization of the primate brain, are necessary to move the field of translational research forward and to bridge the translational gaps. The present studies describe the establishment of a comprehensive battery of touchscreen-based tasks that capture a spectrum of domains sensitive to detecting aging-related cognitive decline, which will provide the greatest benefit through longitudinal evaluation throughout the prolonged lifespan of the marmoset.

摘要

对动物实验结果难以转化至人体的担忧日益凸显,尤其是在啮齿动物模型的认知改善方面,这些改善未能转化为对人类有意义的临床益处。这个问题已得到广泛认可,最近在阿尔茨海默病领域尤为明显,尽管该问题贯穿中枢神经系统(CNS)疾病谱,包括神经发育、神经精神和神经退行性疾病。因此,近期的努力集中在通过纳入更多临床上类似的认知结果测量方法来改善临床前到临床的转化,例如基于触摸屏的检测方法,这种方法可跨物种使用,并且在最小化转化差距方面具有巨大潜力。对于与衰老相关的研究,纳入能够促进对认知衰退开始出现的漫长前驱期进行研究的模型系统也很重要,而认知衰退是短寿命物种(如实验啮齿动物)的一个主要限制因素。我们认为,为了改善认知功能和功能障碍的转化,具有灵长类动物大脑保守解剖和功能组织的非人灵长类动物模型对于推动转化研究领域向前发展以及弥合转化差距是必要的。本研究描述了一系列基于触摸屏的综合任务的建立,这些任务涵盖了对检测与衰老相关的认知衰退敏感的一系列领域,通过在狨猴的整个漫长寿命期间进行纵向评估,将带来最大的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5abd/11039501/6a81ee5162f2/13415_2023_1144_Fig1_HTML.jpg

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