Caregiver experiences during early development profoundly affect development of the brain and behavior. Caregiver maltreatment imparts risk for later cognitive dysfunction and psychiatric disorders. An emerging idea is that epigenetic marking of the genome may underlie the genesis of these outcomes. However, this is based largely on correlational evidence and a causal relationship has not been established. Using a rodent model that we developed, we have shown that caregiver maltreatment induces aberrant methylation of DNA associated with the Brain-derived neurotrophic factor (Bdnf) gene within the prefrontal cortex (hypermethylation), amygdala (hypomethylation), and hippocampus (hypermethylation) of female rats. We have also shown that females when adult exhibit more anxiety-like behavior during gestation and mistreat their own offspring. Finally, we have shown that aberrant cortical Bdnf gene expression and DNA methylation patterns (hypermethylation) induced by caregiver maltreatment are reversible in adulthood by pharmacological manipulation of DNA methylation. The present project will utilize our rodent model to explore the central hypothesis that epigenetic gene changes are a basis for parenting behavior associated with caregiver maltreatment. The goal of the first aim is to determine whether pharmacological manipulation of DNA methylation improves behavior of maltreated-females. The goal of the second aim is to determine whether treatment of females with a demethylating agent at the time of maltreatment can prevent the emergence of aberrant methylation and maternal behavior. Finally, the goal of the third aim is to characterize gene-specific DNA methylation patterns in maltreated-females in brain regions associated with maternal behavior. These studies provide an innovative and informative approach for understanding the epigenetic consequences of exposure to an adverse caregiving environment. Furthermore, data generated from these studies will be the first to empirically establish a causal link between maltreatment-induced DNA methylation alterations and parenting behavior.

Public Health Relevance

This project explores an innovative hypothesis in evaluating the effects of maltreatment on maternal behavior and epigenetic mechanisms, giving us novel insight into typical and atypical behavioral development in females. This proposal will advance public health by elucidating molecular mechanisms of brain development relevant to the perpetuation of abusive caregiving.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD087509-01
Application #
9080464
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Freund, Lisa S
Project Start
2016-09-22
Project End
2021-08-31
Budget Start
2016-09-22
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$291,330
Indirect Cost
$104,580
Name
University of Delaware
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716