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|Title:||VARIATIONS IN MATERNAL CARE EARLY IN LIFE MODULATE THE EXPRESSION OF AMPA AND NMDA RECEPTOR SUBUNITS.|
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|Authors/Affiliations:||1 Mathieu Parent*; 1 Josie Diorio; 1 Michael J. Meaney; |
1 Douglas Hospital Research Center, McGill University, Montreal, QC, Canada.
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|Content:||Natural variations in maternal behaviour during the first post-natal week have an enduring influence on development and function of the hippocampus (Liu et al., 2000). Previous experiments in our lab have shown that the amount of maternal licking and grooming (LG) received during the first 6 days of life modulates offspring behaviour and gene expression into adulthood. As adults, animals that received high levels of LG (highs) show increased hippocampal synaptogenesis and enhanced mRNA expression of NMDA and AMPA receptor subunits relative to animals that received low levels of LG (lows) and these effects are associated with differences in hippocampal learning (Liu et al., 2000; Bredy et al., 2003; 2004). However, it is not known how maternal care produces these sustained changes of expression. Other research from our lab has shown that differences in maternal care are associated with alterations in methylation status of promoter regions for differentially expressed genes in highs and lows (e.g. Weaver et al., 2004; Champagne et al. 2006). We are therefore currently examining the potential role of epigenetic modifications in the differential expression of AMPA and NMDA subunits in high and low offspring.|
Since we have previously shown epigenetic modifications resulting from maternal care after the first week of life, we hypothesized that the differences in expression of NMDA and AMPA receptor subunits should be detectable as early as post-natal day 6 and that these differences should be accompanied by changes in the methylation and acetylation pattern of their promoters. Our primary objective is to comprehensively analyse the expression of NMDA and AMPA subunits in the hippocampus at P6. Targets showing differential modulation by maternal care will then be analysed for differences in DNA methylation and histone acetylation.
Material and Methods
Maternal behaviour is observed for five 72 minutes observation periods per day for the first six days postpartum (Myers et al., 1989, Liu et al., 1997, Francis et al., 1999) Expression of the various subunits of NMDA and AMPA receptors was analysed using qRT-PCR. The protein levels were confirmed using Western blotting and immunoprecipitation. Promoter analysis focused on binding sites of transcription factors such as Sp-1 and NGFI-A using chromatin immunoprecipitation and bisulphite mapping.
Variations in maternal care had a direct influence on the expression pattern of the NMDA and AMPA receptor subunits. We found that as early as six days postpartum, the pattern of mRNA expression was significantly different in the hippocampus of highs compared to lows. Preliminary data on the methylation status of relevant promoters will also be presented.
Maternal care has a strong effect on gene expression, learning, and memory. These effects can persist through adulthood. Here, we show that the learning and memory transcriptome can be modulated within the first week of life by an environmental factor, maternal care.
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