Maternal separation with early weaning: a rodent model providing novel insights into neglect associated developmental deficits.
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.
Yale University School of Medicine, CT, USA. becky.carlyle@yale.edu
Becky C
BC
Carlyle
Alvaro
A
Duque
Robert R
RR
Kitchen
Kelly A
KA
Bordner
Daniel
D
Coman
Eliza
E
Doolittle
Xenophonios
X
Papademetris
Fahmeed
F
Hyder
Jane R
JR
Taylor
Arthur A
AA
Simen
D000818:Animals; D001007:Anxiety; D001288:Attention; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D002649:Child Abuse / Q000523:psychology; D047369:Chromatin Immunoprecipitation; D002658:Developmental Disabilities / Q000235:genetics / Q000523:psychology; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D006801:Humans; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D017397:Prefrontal Cortex / Q000378:metabolism / Q000503:physiopathology; D040901:Proteomics; D012313:RNA / Q000032:analysis; D014886:Weaning
D012313:RNA