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Differential Pattern of Global DNA Methylation at Two Time Points in Brain Regions of AS/AGU Rats Compared with AS Rats

By Sohair Mohammed Khojah, Dagmara McGuinness, Paul G. Shiels and Anthony Payne


DNA methylation is a critical epigenetic modification involved in the saptio-temporal and developmental regulation of the genome. It is thought to provide a degree of plasticity for the genome in response to environmental stresses, whose effects can span generations. Notably, the methylation process has been demonstrated to be highly reactive to a variety of factors, including diet and maternal in-utero stress. DNA methylation has also been shown to be important in the functioning of the brain. The dopamine signalling pathway is tightly regulated by the methylation of the promoter regions of two key factors: tyrosine hydroxylase (a precursor in the synthesis of dopamine) and the dopamine transporter. We have explored the impact of methylation in the brain, using the AS/AGU rat, a rat model of accelerated ageing with a distinct Parkinsonian phenotype, where disruption of the dopamine signalling system is central to the phenotype and which is driven by a stop mutation in a single gene, that for protein kinase C gamma (PKCγ), in comparison to the parental wild type AS strain. In this model, we have demonstrated differential methylation in specific brain regions that vary with age, coincident with loss of PKCγ expression, and dopamine signalling disruption in AS/AGU rats

Year: 2016
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Provided by: Enlighten
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