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Updated: May 17, 2026
Limited Bedding and Nesting as a Model for Early-Life Adversity in Mice
Published on: July 12, 2024
Maternal separation with early weaning: a rodent model providing novel insights into neglect associated developmental
Becky C Carlyle1, Alvaro Duque, Robert R Kitchen
1Yale University School of Medicine, CT, USA. becky.carlyle@yale.edu
Insights
Early life neglect in mice causes long-term behavioral issues. Molecular profiling reveals novel pathways in protein translation and myelination, offering new targets for understanding neglect
Area of Science:
- Neuroscience
- Developmental Psychology
- Molecular Biology
Background:
- Child neglect is a major public health concern with lasting psychological and behavioral consequences.
- Existing research primarily targets stress response systems like the hypothalamus-pituitary-adrenal axis.
Purpose of the Study:
- To comprehensively profile the molecular underpinnings of early-life neglect using a mouse model.
- To investigate novel molecular pathways affected by neglect.
Main Methods:
- Utilized the maternal separation and early weaning mouse model.
- Employed chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses.
- Conducted RNA profiling and label-free proteomics.
Main Results:
- Validated the maternal separation and early weaning model for reflecting human neglect-related behavioral deficits (hyperactivity, anxiety, attention deficits).
- Identified protein translation and myelination as significantly altered molecular pathways.
- Generated comprehensive molecular profiles of neglected mice.
Conclusions:
- The maternal separation and early weaning model is a valid tool for studying early-life neglect.
- Protein translation and myelination represent novel molecular targets for understanding the long-term effects of child neglect.
- Molecular profiling provides insights into the biological mechanisms underlying neglect-induced deficits.
Abstract:
Child neglect is the most prevalent form of child maltreatment in the United States, and poses a serious public health concern. Children who survive such episodes go on to experience long-lasting psychological and behavioral problems, including higher rates of post-traumatic stress disorder symptoms, depression, alcohol and drug abuse, attention-deficit/hyperactivity disorder, and cognitive deficits. To date, most research into the causes of these life-long problems has focused on well-established targets such as stress responsive systems, including the hypothalamus-pituitary-adrenal axis. Using the maternal separation and early weaning model, we have attempted to provide comprehensive molecular profiling of a model of early-life neglect in an organism amenable to genomic manipulation: the mouse. In this article, we report new findings generated with this model using chromatin immunoprecipitation sequencing, diffuse tensor magnetic resonance imaging, and behavioral analyses. We also review the validity of the maternal separation and early weaning model, which reflects behavioral deficits observed in neglected humans including hyperactivity, anxiety, and attentional deficits. Finally, we summarize the molecular characterization of these animals, including RNA profiling and label-free proteomics, which highlight protein translation and myelination as novel pathways of interest.
