Rethinking the Approach to Preclinical Models of Anorexia Nervosa.

Rethinking the Approach to Preclinical Models of Anorexia Nervosa.
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DOI:
10.1007/s11920-022-01319-2
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发表时间:
2022-01
影响因子:
6.7
通讯作者:
Zeltser LM
Zeltser LM
中科院分区:
医学2区
文献类型:
--
作者:
François M;Zeltser LM

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这篇综述的目的是描述如何利用临床前动物研究中的新兴技术发展来加速神经性厌食症(AN)的研究。基于活动的厌食症(阿坝)的范例,最好的表征动物模型的AN,结合限制喂养,过度运动,和体重减轻。越来越多的证据支持这一观点,即该模型中的病理生理学体重减轻是由于AN的一个临床特征--认知障碍。有针对性的操作,概括了大脑的变化,报告在AN -多巴胺能亢进或过度活跃的皮质输入到丘脑核-加剧了阿坝范式的体重减轻,提供了第一个证据的因果关系。临床前研究的力量在于能够评估临床研究中涉及的神经元回路的靶向操作的后果。需要额外的范例来捕获在阿坝中看不到的AN的其他特征。
The goal of this review is to describe how emerging technological developments in pre-clinical animal research can be harnessed to accelerate research in anorexia nervosa (AN). The activity-based anorexia (ABA) paradigm, the best characterized animal model of AN, combines restricted feeding, excessive exercise, and weight loss. A growing body of evidence supports the idea that pathophysiological weight loss in this model is due to cognitive inflexibility, a clinical feature of AN. Targeted manipulations that recapitulate brain changes reported in AN — hyperdopaminergia or hyperactivity of cortical inputs to the nucleus accumbens — exacerbate weight loss in the ABA paradigm, providing the first evidence of causality. The power of preclinical research lies in the ability to assess the consequences of targeted manipulations of neuronal circuits that have been implicated in clinical research. Additional paradigms are needed to capture other features of AN that are not seen in ABA.
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