Talpos John, Steckler Thomas
Janssen Research & Development, Turnhoutseweg 30, 2340, Beerse, Belgium.
Cell Tissue Res. 2013 Oct;354(1):297-308. doi: 10.1007/s00441-013-1694-7. Epub 2013 Aug 16.
During the last decade, the idea of a "translational" approach has become commonplace within the field of neuroscience. Despite the rapid adaptation of this theoretical framework, few examples of hypothesis-driven translation start with a pre-clinical finding and end with a positive clinical result and no examples of a novel medication have been developed in this way for the treatment of cognition-related disorders. Whereas instances of successful translation exist, most of these are the result of post-hoc hypothesis testing, rather than a priori hypothesis creation. Indeed, part of this disconnection between pre-clinical and clinical results has been driven by paradigms used at both the pre-clinical level (measurement of behaviors that might not be relevant to a patient population) and the clinical level (use of test batteries that cannot be modeled in a pre-clinical environment). However, automated cognition batteries that require responses to stimuli displayed upon a video monitor are decreasing the distance between pre-clinical and clinical behavioral studies. In the last 5 years, numerous papers have been published demonstrating that cognitive functions can be measured in a similar manner in the rodent as in a clinical setting via touch-screen-equipped operant boxes. Here, we argue that the touch-screen approach has the potential of being a powerful tool for the translation of pre-clinical hypotheses into positive clinical findings.
在过去十年间,“转化”方法的理念在神经科学领域已变得司空见惯。尽管这一理论框架迅速得到应用,但很少有假设驱动的转化实例是从临床前发现开始并以积极的临床结果告终的,而且还没有以这种方式开发出用于治疗认知相关障碍的新型药物。虽然存在成功转化的实例,但其中大多数是事后假设检验的结果,而非先验假设的创建。事实上,临床前和临床结果之间这种脱节的部分原因在于临床前层面(测量可能与患者群体无关的行为)和临床层面(使用无法在临床前环境中建模的测试组合)所采用的范式。然而,需要对视频监视器上显示的刺激做出反应的自动化认知测试组合正在缩小临床前和临床行为研究之间的差距。在过去五年中,已发表了大量论文,表明通过配备触摸屏的操作性实验箱,在啮齿动物中测量认知功能的方式可以与临床环境中类似。在此,我们认为触摸屏方法有潜力成为将临床前假设转化为积极临床发现的有力工具。