Neuroscience Institute, Georgia State University.
Neuroscience Institute, Georgia State University;
J Vis Exp. 2024 Jul 12(209). doi: 10.3791/66879.
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.
早期生活逆境（ELA），如虐待、忽视、缺乏资源和不可预测的家庭环境，是导致神经精神障碍（如抑郁症）的已知风险因素。用于研究慢性应激对大脑发育影响的 ELA 动物模型，通常依赖于操纵母体照顾的质量和/或数量，因为这是哺乳动物（包括人类）早期生活经历的主要来源。这里提供了一种在小鼠中使用有限垫料和巢穴（LBN）模型的详细方案。该模型模拟了一种资源匮乏的环境，通过限制给予母鼠用于为其幼崽筑巢的垫料量，并通过笼子中的网格平台将小鼠与垫料隔开，在关键发育窗口（产后第 2-9 天）引发了母体照顾的碎片化和不可预测模式。提供了代表性数据来说明 LBN 模型导致的母体行为变化，以及幼鼠体重减轻和基础皮质酮水平的长期变化。在成年期，在 LBN 环境中饲养的后代表现出异常的应激反应、认知缺陷和快感缺失样行为。因此，该模型是一种重要的工具，可以定义 ELA 如何改变应激敏感脑回路的成熟度，并导致导致易患精神障碍的长期行为变化。
