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转化神经科学中的小鼠:我们在做什么?

Mice in translational neuroscience: What R we doing?

作者信息

Azkona Garikoitz, Sanchez-Pernaute Rosario

机构信息

Department of Basic Psychological Processes and Their Development-School of Psychology, University of the Basque Country (UPV/EHU), San Sebastian, Spain.

Andalusian Network for the Design and Translation of Advanced Therapies, Andalusian Health Ministry, Sevilla, Spain.

出版信息

Prog Neurobiol. 2022 Oct;217:102330. doi: 10.1016/j.pneurobio.2022.102330. Epub 2022 Jul 21.

Abstract

Animal models play a pivotal role in translational neuroscience but recurrent problems in data collection, analyses, and interpretation, lack of biomarkers, and a tendency to over-reliance on mice have marred neuroscience progress, leading to one of the highest attrition rates in drug translation. Global initiatives to improve reproducibility and model selection are being implemented. Notwithstanding, mice are still the preferred animal species to model human brain disorders even when the translation has been shown to be limited. Non-human primates are better positioned to provide relevant translational information because of their higher brain complexity and homology to humans. Among others, lack of resources and formal training, strict legislation, and ethical issues may impede broad access to large animals. We propose that instead of increasingly restrictive legislation, more resources for training, education, husbandry, and data sharing are urgently needed. The creation of multidisciplinary teams, in which veterinarians need to play a key role, would be critical to improve translational efficiency. Furthermore, it is not usually acknowledged by researchers and regulators the value of comparative studies in lower species, that are instrumental in toxicology, target identification, and mechanistic studies. Overall, we highlight here the need for a conceptual shift in neuroscience research and policies to reach the patients.

摘要

动物模型在转化神经科学中起着关键作用,但数据收集、分析和解释方面反复出现的问题、生物标志物的缺乏以及对小鼠的过度依赖倾向阻碍了神经科学的进展,导致药物转化中的损耗率居高不下。目前正在实施提高可重复性和模型选择的全球倡议。尽管如此,即使已证明小鼠在转化方面存在局限性,但它们仍是模拟人类脑部疾病的首选动物物种。由于非人类灵长类动物具有更高的大脑复杂性和与人类的同源性,它们更有能力提供相关的转化信息。除此之外,资源和正规培训的缺乏、严格的立法以及伦理问题可能会阻碍对大型动物的广泛使用。我们建议,迫切需要的是更多用于培训、教育、饲养和数据共享的资源,而不是日益严格的立法。创建多学科团队(兽医需要在其中发挥关键作用)对于提高转化效率至关重要。此外,研究人员和监管机构通常没有认识到在低等物种中进行比较研究的价值,而这种研究在毒理学、靶点识别和机制研究中很有帮助。总体而言,我们在此强调神经科学研究和政策需要进行观念转变,以惠及患者。

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