Tulane University Medical School, Department of Pharmacology and Neuroscience Program , Tulane Neurophenotyping Platform, SL-83, 1430 Tulane Ave, New Orleans, LA 70112 , USA +1 504 988 3354 ;
Expert Opin Drug Discov. 2011 Jul;6(7):755-69. doi: 10.1517/17460441.2011.586028. Epub 2011 Jun 6.
Animal behavioral models have become an indispensable tool for studying anxiety disorders and testing anxiety-modulating drugs. However, significant methodological and conceptual challenges affect the translational validity and accurate behavioral dissection in such models. They are also often limited to individual behavioral domains and fail to target the disorder's real clinical picture (its spectrum or overlap with other disorders), which hinder screening and development of novel anxiolytic drugs.
In this article, the authors discuss and emphasize the importance of high-throughput multi-domain neurophenotyping based on the latest developments in video-tracking and bioinformatics. Additionally, the authors also explain how bioinformatics can provide new insight into the neural substrates of brain disorders and its benefit for drug discovery.
The throughput and utility of animal models of anxiety and other brain disorders can be markedly increased by a number of ways: i) analyzing systems of several domains and their interplay in a wider spectrum of model species; ii) using a larger number of end points generated by video-tracking tools; iii) correlating behavioral data with genomic, proteomic and other physiologically relevant markers using online databases and iv) creating molecular network-based models of anxiety to identify new targets for drug design and discovery. Experimental models utilizing bioinformatics tools and online databases will not only improve our understanding of both gene-behavior interactions and complex trait interconnectivity but also highlight new targets for novel anxiolytic drugs.
动物行为模型已成为研究焦虑症和测试焦虑调节药物不可或缺的工具。然而,这些模型在转化有效性和准确的行为剖析方面存在重大的方法学和概念性挑战。它们通常也仅限于单个行为领域,无法针对该疾病的真实临床情况(其与其他疾病的范围或重叠),这阻碍了新型抗焦虑药物的筛选和开发。
本文作者讨论并强调了基于视频追踪和生物信息学最新进展的高通量多领域神经表型分析的重要性。此外,作者还解释了生物信息学如何为大脑疾病的神经基础提供新的见解及其对药物发现的益处。
通过以下几种方式,可以显著提高焦虑和其他大脑疾病动物模型的通量和效用:i)分析更广泛的模型物种中多个领域及其相互作用的系统;ii)使用视频追踪工具生成更多的终点;iii)使用在线数据库将行为数据与基因组、蛋白质组和其他生理相关标记物相关联;iv)创建基于分子网络的焦虑模型,以确定药物设计和发现的新靶点。利用生物信息学工具和在线数据库的实验模型不仅将提高我们对基因-行为相互作用和复杂性状相互联系的理解,还将突出新型抗焦虑药物的新靶点。