Abstract
Depression is one of the most common psychiatric disorders affecting public health. Studies over the past years suggest that the methylations of some specific genes such as BDNF, SLC6A4, and NR3C1 play an important role in the development of depression. Recently, epigenetic evidences suggest that the expression levels of DNA methyltransferases differ in several brain areas including the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens in depression patients and animal models, but the potential link between the expression levels of DNA methylatransferases and the methylations of specific genes needs further investigation to clarify the pathogenesis of depression.
Highlights
Depression, known as major depressive disorder (MDD), is a common chronic and recurrent mental disorder characterized by at least two weeks of presenting with low mood and aversion to daily activities, which affect normal social life [1]
It makes a model of gene-environment interaction for the pathogenesis of MDD (Figure 1), where the DNA methylation changes of genes in HPA axis are adaptive to the stress stimulation, which are reversible once the stress is removed; it induces depression though if the stressor stays for a long period
Sales et al found that systematic injection of DNA methylation inhibitors (5-AzaD and RG108) into depressed mice could rescue the despair-like behavior and effectively relieve hypermethylation in hippocampus and prefrontal cortex caused by stress [101]
Summary
Depression, known as major depressive disorder (MDD), is a common chronic and recurrent mental disorder characterized by at least two weeks of presenting with low mood and aversion to daily activities, which affect normal social life [1]. They mainly distributed in the ventricular zone, subventricular zone, hippocampus and amygdala, where the neural stem cells locate [23] Consistent with these observations in human and primates, a recent study in rats showed that the mRNA expression of Dnmt3l in the hypothalamus and hippocampus followed a pattern opposite to the other Dnmts, that was low expression in newborns and increasing expression with age [66]. This indicates DNMT3L may function differently compared with other DNMTs, important in neurogenesis and neural plasticity, which are essential processes during brain maturation, a stage when the prevalence of early-onset depression is high.
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