Name: Video: Inducing Early-Life Adversity Using the Limited Bedding and Nesting Paradigm in Mouse Models
Uploaded: 2024-07-12T14:25:00
Description: 67 Views. Inducing Early-Life Adversity Using the Limited Bedding and Nesting Paradigm in Mouse Models

inducing early-life adversity using the limited bedding and nesting paradigm in mouse models

Modeling Early-Life Adversity in Mice Using Limited Bedding and Nesting

The early postnatal period is a critical developmental window in which environmental influences can shift the trajectory of development. For example, early-life adversity (ELA) can alter brain development to provoke long-term changes in cognitive and emotional function. Examples of ELA include physical or emotional abuse, neglect, inadequate resources, and an unpredictable home environment occurring during childhood or adolescence1. It is known that ELA is a risk factor for developing disorders such as depression, substance use disorder, post-traumatic stress disorder (PTSD), and anxiety2,3,4,5. This is important given that the levels of childhood poverty in the US have more than doubled recently, from 5.2% in 2021 to 12.4% in 20226, and although poverty itself is not necessarily ELA, it does increase the probability of various types of ELA7.
Animal models have long been essential for understanding the effects of early-life stress on brain development and adult outcomes. The two main animal models used in recent years to dissect this phenomenon are maternal separation (MS) and an impoverished environment induced by limited bedding and nesting materials (LBN). MS was developed as a model of parental deprivation8. In it, rodent dams are taken away from their pups, usually for several hours, every day until weaning8. The MS paradigm has been found to result in depressive- and anxiety-like behaviors in adulthood9, as well as an aberrant response to chronic stress10,11. On the other hand, the LBN model, first developed in the Baram laboratory12, does not separate the dam from the pups, but rather modifies the environment in which the pups are reared, mimicking a low-resource environment12,13. Decreasing the amount of nesting material and preventing direct access to the bedding in this model results in disrupted maternal care from the dams3. Since robust and predictable maternal care is required for the proper development of cognitive and emotional brain circuits14, fragmented maternal care from LBN can result in a range of outcomes, including an over-active Hypothalamic-Pituitary-Adrenal (HPA) axis, shifted excitatory-inhibitory balance in multiple brain regions, increased corticotropin-releasing hormone (CRH) levels, and depressive-like behavior in the offspring13,15,16,17,18,19.
The exact mechanism by which ELA results in increased risk for neuropsychiatric disorders is not completely understood. It is thought to be related to alterations in the HPA axis circuitry19,20, and recent evidence shows that this may be caused by changes in microglial synaptic pruning19. The LBN model has been shown to be a crucial tool for understanding the perinatal environment&#39;s impact on brain development and long-term behavioral outcomes. Although this model was initially developed for rats, it has also been adapted for mice in order to take advantage of the existing transgenic tools12,13. Notably, the model is very similar in both species and provokes highly convergent outcomes, such as alterations in the HPA axis, cognitive deficits,&#160;and depressive-like behavior, thus highlighting its cross-species utility and translational potential. This article will provide a detailed description of how to employ the limited bedding and nesting model in mice, collecting and analyzing maternal behavior and offspring outcomes to validate the model&#39;s efficacy and the expected results.

Author Spotlight: Exploring Microglial Interactions with Stress-Response Circuitry Using the Limited Bedding and Nesting Model

Limited Bedding and Nesting as a Model for Early-Life Adversity in Mice

Inducing Early-Life Adversity Using the Limited Bedding and Nesting Paradigm in Mouse Models

inducing-early-life-adversity-using-limited-bedding-nesting-paradigm

Research

JoVE Journal

Neuroscience

67 Views. Inducing Early-Life Adversity Using the Limited Bedding and Nesting Paradigm in Mouse Models

Video: Inducing Early-Life Adversity Using the Limited Bedding and Nesting Paradigm in Mouse Models

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&#160;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.

This protocol describes an animal model for studying how early-life adversity, provoked by an impoverished environment and unpredictable maternal care during the early postnatal period, affects brain development and the future risk of mental disorders.

Early-life adversity (ELA), such as abuse, neglect, lack of resources, and an unpredictable home environment, is a known risk factor for developing ...

Methods Article

Inducing Early-Life Adversity Using the Limited Bedding and Nesting Paradigm in Mouse Models