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动物模型与人类神经精神疾病

Animal models and human neuropsychiatric disorders.

作者信息

Fisch Gene S

机构信息

Yeshiva University, 875 West End Ave. Apt 6B, New York, NY 10025, USA.

出版信息

Behav Genet. 2007 Jan;37(1):1-10. doi: 10.1007/s10519-006-9117-0. Epub 2006 Oct 18.

Abstract

Humans have long distinguished themselves from other living organisms. Therefore, to make use of animal models for neuropsychiatric disorders, it is important to acknowledge what has changed historically. Darwin argued that there was continuity in mind between humans and nonhuman species, and animal experimental psychologists and others have debated the existence of consciousness and mentality in animals ever since. Those trained in the associationist tradition sought to eliminate the concept of mind in favor of an empiricial, behavioral approach; others trained in the introspectionist tradition sought to include mental abilities as an integral part of comparative animal psychology. The waning of behaviorism and ascendance of cognitive psychology in the mid-twentieth century renewed interest in the notion of consciousness and mind in nonhuman organisms, particularly as they related to learning impairment and neurobehavioral disorders. Moreover, advances in molecular genetics and technology facilitated development of genetically modified mouse strains that could be used to examine cognitive deficits and psychopathology. However, genetic modifications to individual genes that produce behavioral dysfunction in the mouse have not always provided clear results. In part, this is likely due to the influence of genes in addition to the targeted gene, sometimes resulting in paradoxical effects. I also examine other issues created by the use of nonhuman models of human disorders, including: language, the effect of background genetic strains, genetic-environmental interactions, and the problems associated with the complex genetics needed to produce similarly complex behavioral phenotypes.

摘要

长期以来,人类一直将自己与其他生物区分开来。因此,为了利用动物模型研究神经精神疾病,认识历史上发生的变化很重要。达尔文认为人类与非人类物种在思维上存在连续性,从那时起,动物实验心理学家和其他人就一直在争论动物是否存在意识和心理。那些接受联想主义传统训练的人试图摒弃心理概念,转而支持经验主义的行为方法;而那些接受内省主义传统训练的人则试图将心理能力纳入比较动物心理学的一个组成部分。20世纪中叶行为主义的衰落和认知心理学的兴起,重新引发了人们对非人类生物意识和心理概念的兴趣,尤其是它们与学习障碍和神经行为障碍的关系。此外,分子遗传学和技术的进步促进了转基因小鼠品系的发展,这些品系可用于研究认知缺陷和精神病理学。然而,对单个基因进行基因改造以在小鼠中产生行为功能障碍并不总是能得到明确的结果。部分原因可能是除了目标基因外,其他基因也有影响,有时会产生矛盾的效果。我还研究了使用人类疾病的非人类模型所产生的其他问题,包括:语言、背景基因品系的影响、基因-环境相互作用,以及与产生同样复杂行为表型所需的复杂遗传学相关的问题。

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