Aberrant DNA methylation and parenting behavior associated with caregiver maltreatment

与照顾者虐待相关的异常 DNA 甲基化和养育行为

基本信息

批准号：
9753763
负责人：
Tania Lynn Roth
金额：
$ 32.37万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-22 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753763
关键词：
Aberrant DNA Methylation Adult Adverse event Affect Amygdaloid structure Animals Automobile Driving Behavior Behavioral Behavioral Mechanisms Biochemical Brain Brain region Brain-Derived Neurotrophic Factor Candidate Disease Gene Caregivers Child Abuse and Neglect Child Rearing Chromatin Cytosine DNA Methylation DNA Sequence Data Development Drug vehicle Environment Enzymes Epigenetic Process Exhibits Exposure to Female Future Gene Expression Gene Expression Alteration Gene Expression Regulation Genes Genetic Fingerprintings Genome Genomic DNA Goals Hippocampus (Brain)Histone Deacetylase Histone Deacetylase Inhibitor Hypermethylation Impaired cognition Individual Infant Intervention Link Maternal Behavior Measures Medial Mediating Mediator of activation protein Memory Mental disorders Methylation Molecular Moods Neuronal Plasticity Nucleus Accumbens Oral Outcome Pharmacology Play Postpartum Period Prefrontal Cortex Pregnancy Preoptic Areas Process Psychopathology Public Health Rattus Regimen Rewards Risk Rodent Model Role Sodium Butyrate Stroke Synaptic plasticity Testing Time Ventral Tegmental Area Work Zebularine anxiety-like behavior base behavioral outcome brain behavior caregiving cohort efficacy testing epigenetic regulation experience genomic RNA improved innovation insight maltreatment methylation pattern mood regulation neurodevelopment novel offspring postnatal prevent public health relevance

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：开发过程中的照料者经验深刻影响大脑的发展和行为的发展。我们已经确定了与脑衍生的神经营养因子（BDNF）基因相关的DNA的异常甲基化，我们已经确定了。 - 在妊娠期间的行为和自己的后代误会。与护理人员虐待有关的育儿行为的基础。孕妇的行为是第三个目标是与孕产妇行为相关的虐待女性。诱导的DNA甲基化改变和育儿行为。