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Chunk #68 — Reversal of the maternal effect on GR expression and HPA responses to stress

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Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome.
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eliminates the effect of maternal care. As expected, enhanced NGFIA binding to the exon 17 promoter increased hippocampal GR expression. Hippocampal GR expression in the TSA-treated adult offspring of low-LG mothers was indistinguishable from that of the high-LG groups. Most important, TSA infusion eliminated the effect of maternal care on HPA responses to stress. During and following exposure to acute stress, plasma corticosterone levels in TSA-treated offspring of low-LG mothers are indistinguishable from those of TSA- or vehicle-treated high-LG mothers. There was no effect of TSA on any measure in the offspring of high-LG animals. This is understandable since under normal circumstances there is considerable H3 acetylation and NGFIA binding at the exon 17 sequence in these animals. Interestingly, TSA treatment also led to the demethylation of the 5' CpG of the NGFIA response element of the GR exon 17 promoter sequence.