Wallace Tanya L, Ballard Theresa M, Glavis-Bloom Courtney
Center for Neuroscience, SRI International, Menlo Park, CA, USA,
Handb Exp Pharmacol. 2015;228:27-57. doi: 10.1007/978-3-319-16522-6_2.
Cognition is a complex brain function that represents processes such as learning and memory, attention, working memory, and executive functions amongst others. Impairments in cognition are prevalent in many neuropsychiatric and neurological disorders with few viable treatment options. The development of new therapies is challenging, and poor efficacy in clinical development continues to be one of the most consistent reasons compounds fail to advance, suggesting that traditional animal models are not predictive of human conditions and behavior. An effort to improve the construct validity of neuropsychological testing across species with the intent of facilitating therapeutic development has been strengthening over recent years. With an emphasis on understanding the underlying biology, optimizing the use of appropriate systems (e.g., transgenic animals) to model targeted disease states, and incorporating non-rodent species (e.g., non-human primates) that may enable a closer comparison to humans, an improvement in the translatability of the results will be possible. This chapter focuses on some promising translational cognitive paradigms for use in rodents, non-human primates, and humans.
认知是一种复杂的大脑功能,它代表着学习与记忆、注意力、工作记忆以及执行功能等诸多过程。认知障碍在许多神经精神疾病和神经疾病中普遍存在,而可行的治疗选择却很少。新疗法的开发具有挑战性,临床开发中疗效不佳仍然是化合物未能推进的最常见原因之一,这表明传统动物模型无法预测人类状况和行为。近年来,为提高跨物种神经心理学测试的结构效度以促进治疗开发所做的努力一直在加强。通过强调理解潜在生物学机制、优化使用合适的系统(如转基因动物)来模拟靶向疾病状态,以及纳入可能更接近人类的非啮齿动物物种(如非人类灵长类动物),结果的可转化性将有可能得到提高。本章重点介绍一些有望用于啮齿动物、非人类灵长类动物和人类的转化性认知范式。