April 9- Epigenetic programing by Maternal Behaviour

April 9- Epigenetic programing by Maternal Behaviour - Adil...

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Adil Geresu Ernie Lin Rudi Lin
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Outline
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Introduction
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Goal of this Study To investigate the epigenetic effects of maternal care on the stress response in their offspring
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What is Epigenetics? Epi – ‘over/above’ the genome Study of phenotypic changes that occur without changing the genomic nucleotide sequence Inherited by at least one successive generation Possible through means such as DNA methylation and chromatin remodeling
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DNA methylation and Chromatin Remodeling Methyl groups typically added at CpG sites CpG stands for cytosine-phosphate- guanosine (DNA methyltransferase detects CpG and methylates the cytosine) Weaver et al. 2004
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DNA methylation and Chromatin Remodeling Level of methylation in a region determines its transcriptional activity Methylation is considered a highly stable, permanent epigenetic mark that will last for the rest of the individual’s life Low methylation correlates with high histone acetylation
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DNA methylation and Chromatin Remodeling Histone acetylation reduces its association with the DNA strand and remodels the chromatin allowing for more open access to the DNA by transcription factors and polymerases http://missinglink.ucsf.edu/lm/genes_and_genomes/acetylation.html
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Study Organism Long-Evans hooded rats Has a large body of research directed at epigenetic & behavioural studies http://www.life.illinois.edu/clockworks/pages/Long-Evans%20Rat.html
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Maternal Behaviour in Rats Weaver et al. looked at maternal behaviour-induced epigenetic effects in the rat model. Noted maternal behaviours: Licking and grooming (LG) Arched-back nursing (ABN) Two major observed groups in nature: low-LG-ABN and high-LG-ABN Variation in maternal care only observed within the first week of postnatal life
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Maternal Behaviour in Rats Previous studies show that these variations in maternal behaviour are correlated with the development of differences in the hypothalamic- pituitary-adrenal (HPA) response to stress in the offspring http://www.awionline.org/www.awionline.org/pubs/cq02/rat-3.jpg
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Maternal Behaviour in Rats Offspring of high-LG-ABN mothers are less fearful and show more modest HPA responses to stress compared to offspring of low-LG-ABN mothers Offspring of low-LG-ABN mothers reared by high-LG-ABN dams resemble the normal offspring of high-LG-ABN mothers (and vice versa) Variations in maternal behavior can serve as a mechanism for the non-genomic transmission of individual differences in stress reactivity across generations
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HPA axis and determinants for the magnitude of the stress response Stress response = “fight or flight” response HPA axis activated by stress which releases glucocorticoid hormones Glucocorticoid receptor in the hippocampus is key to negative feedback regulation of HPA activity, and reduces the magnitude of the stress response GR is hypothesized to be the target of the epigenetic factors in this case, modifying its hippocampal expression levels.
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Stress response regulation by hippocampus
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Stress response regulation by hippocampus
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April 9- Epigenetic programing by Maternal Behaviour - Adil...

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