Background: Brain Derived Neurotrophic Factor (BDNF) has been implicated in neuronal survival and plasticity and reported as being involved in various mental illnesses, including attempted and completed suicide. Evidence from postmortem studies has also shown an altered expression of BDNF in suicide victims brains. Association studies for functional polymorphisms in the BDNF gene provided conflicting results. We went one step forward in the analysis of the BDNF gene by also studying epigenetic factors, the inherited and acquired modifications of DNA and histones that modulate gene expression without a change in nuclear DNA sequence. Method: We studied DNA methylation of the BDNF gene in 44 suicide victims and 33 controls. We also analyzed global DNA methylation and quantified mRNA in 12 subjects. Results: We found no significant differences between cases and controls in global DNA methylation. At all 4 studied methylation sites suicide victims had significantly higher methylation than controls. BDNF mRNA was significantly and negatively correlated with methylation. Conclusion: These results suggest that methylation at the selected four sites correspond to a reduction in mRNA transcription and may account for decreased BDNF expression in brains of suicide victims. The study of DNA methylation has the potential to transform our understanding about the molecular aetiology of suicide

Beyond DNA sequence

SARCHIAPONE, Marco
2009

Abstract

Background: Brain Derived Neurotrophic Factor (BDNF) has been implicated in neuronal survival and plasticity and reported as being involved in various mental illnesses, including attempted and completed suicide. Evidence from postmortem studies has also shown an altered expression of BDNF in suicide victims brains. Association studies for functional polymorphisms in the BDNF gene provided conflicting results. We went one step forward in the analysis of the BDNF gene by also studying epigenetic factors, the inherited and acquired modifications of DNA and histones that modulate gene expression without a change in nuclear DNA sequence. Method: We studied DNA methylation of the BDNF gene in 44 suicide victims and 33 controls. We also analyzed global DNA methylation and quantified mRNA in 12 subjects. Results: We found no significant differences between cases and controls in global DNA methylation. At all 4 studied methylation sites suicide victims had significantly higher methylation than controls. BDNF mRNA was significantly and negatively correlated with methylation. Conclusion: These results suggest that methylation at the selected four sites correspond to a reduction in mRNA transcription and may account for decreased BDNF expression in brains of suicide victims. The study of DNA methylation has the potential to transform our understanding about the molecular aetiology of suicide
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11695/16437
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