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Epigenetic Programming By Maternal Behavior

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Laura Zahn

on 5 November 2012

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Transcript of Epigenetic Programming By Maternal Behavior

Laura Zahn Epigenetic Programming By Maternal Behavior Parenting Styles Future Questions Phenotypic changes that occur without changing the genomic nucleotide sequence Epigenetics! Licking, grooming, and arched-back nursing (LG-ABN) Maternal Behavior in Rats As adults, offspring are less fearful EFfects of High LG-ABN Maternal Behavior Other effects of high- versus low-LG-ABN mothering: What's happening here? Important theme in developmental psychology How do these influences become long lasting? Can influence the sort of adult a child becomes Heritable changes in gene expression Possible through chromatin remodeling: Methylation of DNA or histones Acetylation Phosphorylation SUMOylation Ubiquitylation High LG-ABN - rates more than 1 SD above mean Low LG-ABN - rates more than 1 SD below mean Differences only apparent within first week postpartum Figure 2. CHiP Analysis Figure 1. Cytosine methylation of GR promoter Figure 3. CHip Anaylsis using HDAC inhibitor Figure 4. TSA effects on cytosine methylation Figure 5. TSA eliminates the maternal effect on hippocampal GR expression and HPA responses to stress Big Picture Increased hippocampal glucocorticoid receptor (GR) mRNA expression Enhanced glucocorticoid feedback sensitivity Have tighter regulation of the secretion of glucocorticoids Reduced corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in response to acute stress Nerve Growth Factor-Inducible protein A (transcription factor) Increased serotonergic tone in the hippocampus of offspring NGFI-A binds to first exon of GR gene, leading to increased expression by recruiting CRB, a histone acetyl transferase (HAT) Female pups raised by high LG-ABN mothers become high LG-ABN mothers themselves as adults High LG-ABN mothering produces lifelong increases in pups in numbers of receptors in the amygdala for benzodiazepines, which have anti-anxiety properties How does high LG-ABN mothering style regulate methylation in a pup? Are there natural events which could reverse the consequences of early mothering style? Early experience does NOT necessarily equate to destiny! Ian CG Weaver, et al. (2004) Nature Neuroscience, 7, 8, 847-854 Eliminating difference in hippocampal GR levels abolishes the effects of early experience on HPA responses to stress in adulthood Sodium Bisulfite Mapping - converts unmethylated cytosine to uracil while leaving methylated cytosine intact Site 16 is ALWAYS methylated in the offspring of low LG-ABN and rarely methylated in the offspring of high LG-ABN.

In contrast, Site 17 is methylated, regardless of differences in maternal care. Cross-fostering reverses differences in methylation at site 16 A DNA methylation pattern can be established through a behavioral mode of programming - without germ line transmission! Differences in methylation status developed between P1 and P6...the same period when differences in maternal behavior of high- and low- LG-ABN mothers are apparent!
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