早期逆境(ELA),比如虐待,疏忽,缺乏资源,和一个不可预测的家庭环境,是导致神经精神疾病如抑郁症的已知危险因素。ELA的动物模型已用于研究慢性应激对大脑发育的影响,通常依赖于控制产妇护理的质量和/或数量,因为这是哺乳动物早期生命经历的主要来源,包括人类。这里,提供了在小鼠中采用有限铺垫和嵌套(LBN)模型的详细方案。这个模型模仿低资源环境,在关键的发育窗口(出生后第2-9天),通过限制给予大坝的筑巢材料的数量,为幼崽筑巢,并通过网眼平台将小鼠与床上用品分开,从而引发了产妇护理的零散和不可预测的模式。提供代表性数据来说明母亲行为的变化,以及幼崽体重下降和基础皮质酮水平的长期变化,这是LBN模型的结果。作为成年人,在LBN环境中饲养的后代已被证明表现出异常的应激反应,认知缺陷,和快感缺失的行为。因此,该模型是定义ELA如何改变压力敏感性脑回路的成熟并导致长期行为改变的重要工具,这些改变赋予精神障碍易感性.
Early-life adversity (ELA), such as abuse, neglect, lack of resources, and an unpredictable home environment, is a known risk factor for developing neuropsychiatric disorders such as depression. Animal models for ELA have been used to study the impact of chronic stress on brain development, and typically rely on manipulating the quality and/or quantity of maternal care, as this is the major source of early-life experiences in mammals, including humans. Here, a detailed protocol for employing the Limited Bedding and Nesting (LBN) model in mice is provided. This model mimics a low-resource environment, which provokes fragmented and unpredictable patterns of maternal care during a critical developmental window (postnatal days 2-9) by limiting the amount of nesting materials given to the dam to build a nest for her pups and separating the mice from the bedding via a mesh platform in the cage. Representative data are provided to illustrate the changes in maternal behavior, as well as the diminished pup weights and long-term changes in basal corticosterone levels, that result from the LBN model. As adults, offspring reared in the LBN environment have been shown to exhibit an aberrant stress response, cognitive deficits, and anhedonia-like behavior. Therefore, this model is an important tool to define how the maturation of stress-sensitive brain circuits is altered by ELA and results in long-term behavioral changes that confer vulnerability to mental disorders.