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GABAA receptor agonist phenobarbital could rectify the decrease of BrdU+/NeuN+ cells in PRS mice. PRS mice also showed an increased expression of DNA methyltransferase 1 (DNMT1) and an increased binding of DNMT1 to GAD67 promoter region. The treatment with DNMT1 inhibitor 5-aza-deoxycytidine restored the decrease of BrdU+/NeuN+ cells and depression-like behaviors in PRS mice via improving GABAergic system. CONCLUSIONS The present results indicate that epigenetic changes of GABAergic system are responsible for adult hippocampus neurogenesi