Caregiver maltreatment causes altered neuronal DNA methylation in female rodents

被引:37
作者
Blaze, Jennifer [1 ]
Roth, Tania L. [1 ]
机构
[1] Univ Delaware, Newark, DE 19716 USA
关键词
EARLY-LIFE STRESS; MEDIAL PREFRONTAL CORTEX; CORTICOTROPIN-RELEASING HORMONE; INFANT ATTACHMENT SECURITY; BDNF GENE-TRANSCRIPTION; PERIPHERAL-BLOOD CELLS; NEUROTROPHIC-FACTOR; LONG-TERM; MATERNAL-CARE; SEX-DIFFERENCES;
D O I
10.1017/S0954579417000128
中图分类号
B844 [发展心理学(人类心理学)];
学科分类号
040202 ;
摘要
Negative experiences with a caregiver during infancy can result in long-term changes in brain function and behavior, but underlying mechanisms are not well understood. It is our central hypothesis that brain and behavior changes are conferred by early childhood adversity through epigenetic changes involving DNA methylation. Using a rodent model of early-life caregiver maltreatment (involving exposure to an adverse caregiving environment for postnatal days 1-7), we have previously demonstrated abnormal methylation of DNA associated with the brain-derived neurotrophic factor (Bdnf) gene in the medial prefrontal cortex (mPFC) of adult rats. The aim of the current study was to characterize Bdnf DNA methylation in specific cell populations within the mPFC. In the prefrontal cortex, there is approximately twice as many neurons as glia, and studies have recently shown differential and distinctive DNA methylation patterns in neurons versus nonneurons. Here, we extracted nuclei from the mPFC of adult animals that had experienced maltreatment and used fluorescence-activated cell sorting to isolate cell types before performing bisulfite sequencing to estimate methylation of cytosine-guanine sites. Our data indicate that early-life stress induced methylation of DNA associated with Bdnf IV in a cell-type and sex-specific manner. Specifically, females that experienced early-life maltreatment exhibited greater neuronal cytosine-guanine methylation compared to controls, while no changes were detected in Bdnf methylation in males regardless of cell type. These changes localize the specificity of our previous findings to mPFC neurons and highlight the capacity of maltreatment to cause methylation changes that are likely to have functional consequences for neuronal function.
引用
收藏
页码:477 / 489
页数:13
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