Article

DNA methylation of the BDNF gene and its relevance to psychiatric disorders

1] Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan [2] Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Journal of Human Genetics (Impact Factor: 2.53). 06/2013; 58(7). DOI: 10.1038/jhg.2013.65
Source: PubMed

ABSTRACT Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor, which is important for neuronal survival, development and synaptic plasticity. Accumulating evidence suggests that epigenetic modifications of BDNF are associated with the pathophysiology of psychiatric disorders, such as schizophrenia and mood disorders. Patients with psychiatric disorders generally show decreased neural BDNF levels, which are often associated with increased DNA methylation at the specific BDNF promoters. Importantly, observed DNA methylation changes are consistent across tissues including brain and peripheral blood, which suggests potential usefulness of these findings as a biomarker of psychiatric disorders. Here we review DNA methylation characteristics of BDNF promoters of cellular, animal and clinical samples and discuss future perspectives.Journal of Human Genetics advance online publication, 6 June 2013; doi:10.1038/jhg.2013.65.

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Available from: Tempei Ikegame, Aug 20, 2015
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    • "Consistent with reports of tissue specific differences in DNA methylation [Rakyan et al., 2008; Byun et al., 2009; Ghosh et al., 2010], our results suggest that blood and saliva have relatively little epigenetic similarity overall or in candidate genes relevant for psychiatric disorders. Methylation differences in BDNF, FKBP5, NR3C1, and SLC6A4 have been reported in the brain, blood cells, and other tissues [Weaver et al., 2004; McGowan et al., 2009; Sugawara et al., 2011; Ikegame et al., 2013a; Ewald et al., 2014; Guidotti et al., 2014]. "
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    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2015; 168(1). DOI:10.1002/ajmg.b.32278 · 3.27 Impact Factor
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    • "There is growing evidence that DNA methylation has a role in the regulation of several genes including RELN and GAD1, in cortical and hippocampal GABAergic neurons of schizophrenic subjects (Akbarian 2010; Grayson and Guidotti, 2013). Brain-derived neurotrophic factor (BDNF), a principal regulator of survival, development, function and plasticity of neurons, is involved in progression of this pathology (Ikegame et al., 2013). A single-nucleotide polymorphism in the human BDNF gene (Val66Met) has been associated with the development of schizophrenia (Rybakowski 2008). "
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    • "A natural antisense transcript for BDNF has been reported to repress BDNF expression in vivo (Modarresi et al., 2012). BDNF expression has also been increasingly tied to promoter DNA methylation in various models of neurological disease, indicating that even under normal developmental conditions, BDNF promoter methylation may be significantly responsible for neurotrophic levels (Ikegame et al., 2013). Activity-dependent changes in promoter methylation of the BDNF gene (5 mC, CpG methylation) are also thought to mediate the release of a repressive chromatin remodeling protein (mSin3A) from the promoter thereby providing anther epigenetic mechanism of BDNF regulation (Martinowich et al., 2003). "
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