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

Summary

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.

Abstract

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.

Introduction

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 anxiety^2,3

Protocol

All of the procedures involving animals were performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and approved by the Institutional Animal Care and Use Committee from Georgia State University (approval number A24011). The mice were bred and maintained in the Animal Facilities at Georgia State University. The experiments were performed on a C57BL/6J strain during the perinatal period (postnatal day [P] 2-10) and included males and females. The reagents and e.......

Discussion

This article provides a detailed protocol to apply the LBN model in mice. This model is an important tool for understanding how an ethologically and translationally relevant form of chronic stress in early life contributes to the development of neuropsychiatric disorders in the offspring¹³. It is also useful for studying maternal behavior and any changes in the dams' brain from a molecular, neuroendocrine, or circuit-based perspective²⁴. For these types of questions, mu.......

Materials

Name	Company	Catalog Number	Comments
2-inch 4 MP 4x Zoom IR Mini PT Dome Network Camera	Hikvision	DS-2DE2A404IW-DE3(S6)
Amazon Basics Aluminum Light Photography Tripod Stand with Case - Pack of 2, 2.8 - 6.7 Feet, 3.66 Pounds, Black	Amazon		From Amazon
Blue Iris	Blue Iris Security		Optional video management software
CAMVATE 1/4"-20 Mini Ball Head with Ceiling Mount for CCTV & Video Wall Monitors Mount - 1991	Camvate		From Amazon
Corn cob bedding	The Andersons	4B
Cotton nestlet	Ancare	NES3600
Mesh divider	McNICHOLS	4700313244	Standard, Aluminum, Alloy 3003-H14, 3/16" No. .032 Standard (Raised), 70% Open Area
Tendelux DI20 IR Illuminator	Tendelux		From Amazon