Molet Jenny, Maras Pamela M, Avishai-Eliner Sarit, Baram Tallie Z
Department of Anatomy/Neurobiology, University of California-Irvine, Irvine, CA, 92697-4475.
Dev Psychobiol. 2014 Dec;56(8):1675-88. doi: 10.1002/dev.21230. Epub 2014 Jun 9.
A close association between early-life experience and cognitive and emotional outcomes is found in humans. In experimental models, early-life experience can directly influence a number of brain functions long-term. Specifically, and often in concert with genetic background, experience regulates structural and functional maturation of brain circuits and alters individual neuronal function via large-scale changes in gene expression. Because adverse experience during sensitive developmental periods is often associated with neuropsychiatric disease, there is an impetus to create realistic models of distinct early-life experiences. These can then be used to study causality between early-life experiential factors and cognitive and emotional outcomes, and to probe the underlying mechanisms. Although chronic early-life stress has been linked to the emergence of emotional and cognitive disorders later in life, most commonly used rodent models of involve daily maternal separation and hence intermittent early-life stress. We describe here a naturalistic and robust chronic early-life stress model that potently influences cognitive and emotional outcomes. Mice and rats undergoing this stress develop structural and functional deficits in a number of limbic-cortical circuits. Whereas overt pathological memory impairments appear during adulthood, emotional and cognitive vulnerabilities emerge already during adolescence. This naturalistic paradigm, widely adopted around the world, significantly enriches the repertoire of experimental tools available for the study of normal brain maturation and of cognitive and stress-related disorders including depression, autism, post-traumatic stress disorder, and dementia.
在人类中发现早期生活经历与认知和情感结果之间存在密切关联。在实验模型中,早期生活经历可长期直接影响多种脑功能。具体而言,且通常与遗传背景协同作用,经历可调节脑回路的结构和功能成熟,并通过基因表达的大规模变化改变单个神经元的功能。由于敏感发育时期的不良经历常与神经精神疾病相关,因此有动力创建不同早期生活经历的现实模型。然后可利用这些模型研究早期生活经历因素与认知和情感结果之间的因果关系,并探究潜在机制。尽管慢性早期生活应激与后期生活中情绪和认知障碍的出现有关,但最常用的啮齿动物模型涉及每日母婴分离,因此是间歇性早期生活应激。我们在此描述一种自然且强大的慢性早期生活应激模型,该模型有力地影响认知和情感结果。经历这种应激的小鼠和大鼠在多个边缘-皮质回路中出现结构和功能缺陷。虽然明显的病理性记忆损伤在成年期出现,但情绪和认知易损性在青春期就已出现。这种在世界各地广泛采用的自然范式显著丰富了可用于研究正常脑成熟以及包括抑郁症、自闭症、创伤后应激障碍和痴呆症在内的认知和应激相关疾病的实验工具库。