Maternal separation with early weaning: a rodent model providing novel insights into neglect associated developmental deficits

Carlyle, Becky C.; Duque, Alvaro; Kitchen, Robert R.; Bordner, Kelly A.; Coman, Daniel; Doolittle, Eliza; Papademetris, Xenophonios; Hyder, Fahmeed; Taylor, Jane R.; Simen, Arthur A.

doi:10.1017/s095457941200079x

Cited by 80Child Abuse and TraumaStress Responses and CortisolNeuroendocrine regulation and behavior

Maternal separation with early weaning: a rodent model providing novel insights into neglect associated developmental deficits

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Carlyle, Becky C., Duque, Alvaro, Kitchen, Robert R., Bordner, Kelly A., Coman, Daniel, Doolittle, Eliza, Papademetris, Xenophonios, Hyder, Fahmeed +2 more·2012·Development and Psychopathology

DOI 10.1017/s095457941200079xPMC PMC3681803

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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.

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Maternal separation interferes with the mother's postnatal regulatory influence on the animal's physiology and development and is considered by many to be an analog of human child neglect.
“Maternal separation interferes with the postnatal regulatory influence that the mother has on the animal’s physiology and development, and is considered by many to be an analog of human child neglect (Carlyle et al., 2012; Pryce et al., 2005).”
From The effects of early life stress on reward processing (2018) · cites this paper as Carlyle et al., 2012

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DeBellis MD Keshavan MS Clark DB Casey BJ Giedd JN Boring AM 1999 A. E. Bennett Research Award. Developmental traumatology. Part II: Brain development Biological Psychiatry 45 1271 1284 10349033

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The effects of early life stress on reward processing
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“Maternal separation interferes with the postnatal regulatory influence that the mother has on the animal’s physiology and development, and is considered by many to be an analog of human child neglect (Carlyle et al., 2012; Pryce et al., 2005).”
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Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice
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Perineuronal nets, inhibitory interneurons and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity
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Environmental programming of susceptibility and resilience to stress in adulthood in male mice
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A mechanistic look at the effects of adversity early in life on cardiovascular disease risk during adulthood
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Authors: Carlyle, B. C., Duque, A., Kitchen, R. R., Bordner, K. A., Coman, D., Doolittle, E., Papademetris, X., Hyder, F., Taylor, J. R., & Simen, A. A.
Affiliations: Yale University (US)
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author: Carlyle, Becky C.
Simen, Arthur A.
ORCID: Carlyle, Becky C.
Duque, Alvaro
Kitchen, Robert R.
Coman, Daniel
Hyder, Fahmeed
Taylor, Jane R.
Simen, Arthur A.
Venue: Development and Psychopathology
Publisher: Cambridge University Press (CUP)
Published: 2012-10-15
Volume: 24
Issue: 4
Pages: 1401-1416
ISSN: 0954-5794 (ISSN-L)
1469-2198
DOI: 10.1017/s095457941200079x
PMC: PMC3681803
OpenAlex: W2048503594
Cited by: 80
References: 115
Citations by year: 2026: 4 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 11 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 3 · 2015: 11 · 2014: 1 · 2013: 4
FWCI: 5.79
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.cambridge.org/core/terms (unspecified)
Locations: Development and Psychopathology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Alcohol Abuse and Alcoholism (P50-AA-A06377)
National Institute on Aging (K08AG030970)
National Institute on Drug Abuse (DA022251, R03DA022251, DA 018343, P30DA018343)
National Institute of Neurological Disorders and Stroke (P30NS052519, U24NS051869)
Topics: Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords: child neglect, maternal separation, early weaning, childhood adversity, developmental deficits, mouse model, ChIP-seq, RNA profiling, proteomics, myelination, mRNA translation, anxiety, hyperactivity, attention deficits, post-traumatic stress disorder, depression, attention deficit hyperactivity disorder
MeSH terms: Animals, Anxiety, Attention, Behavior, Animal, Brain, Child, Child Abuse, Developmental Disabilities, Disease Models, Animal, Humans, Maternal Deprivation, Mice, Inbred C57BL, RNA, Weaning, Prefrontal Cortex, Proteomics, Epigenesis, Genetic, Chromatin Immunoprecipitation, Mice, Diffusion Tensor Imaging

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Maternal separation with early weaning: a rodent model providing novel insights into neglect associated developmental deficits

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