An Open-Source and Highly Adaptable Rodent Limited Bedding and Nesting Apparatus for Chronic Early Life Stress.

Abstract

Early life stress (ELS) increases susceptibility to cognitive and socioemotional dysfunction by disrupting the neurobiological systems that regulate these behaviors. Animal models provide a valuable tool for investigating the underlying mechanisms, enabling precise manipulation of stress exposure during development. The limited bedding and nesting (LBN) model, which induces maternal stress by restricting access to bedding and nesting materials in rodents, has been instrumental in advancing our understanding of chronic ELS. While this paradigm has been widely adopted, variations in apparatus designs and subtle differences in methodologies could impact consistency across studies. Here, we provide standardized guidelines for a cost-effective open-source mouse LBN apparatus design, which could further enhance the model's utility while supporting pup survival. We additionally present our findings observed during the duration of the LBN paradigm, which spans from postnatal day (PND) 2 to 10, for both dams and pups. We observe comparable corticosterone in control and LBN dams from PND 3 to 5. However, from PND 6 to 10, corticosterone remains elevated in LBN dams, while control dams show a decline. Notably, the LBN paradigm disrupts maternal care, as LBN dams exhibit more frequent nest exits and stereotypic behaviors during the dark phase. At PND 10, pups exhibit significantly reduced blood serum corticosterone levels and lower body weight compared with those reared under control conditions. By providing open-source equipment and detailed experimental protocols, our work aims to build on existing LBN paradigms to further enhance the accessibility and reproducibility of chronic ELS models.