Abstract
Early-life stress affects brain development and contributes to psychiatric disorders. Adult neurogenesis in the dentate gyrus (DG) is also involved in psychiatric disorders and early-life stress decreases adult neurogenesis in DG. These suggest that early-life stress might contribute to psychiatric disorders via adult neurogenesis in DG. Here we examined the effects of maternal separation (MS) in early-life on adult rat DG-derived neural precursors (ADP) . In MS group, pups were separated from mothers for 3 hours daily from postnatal day (PND) 2 to 14. At PND 56, ADP were isolated from both groups. Effects of MS on ADP were examined with immunocytochemistry. An epigenetic mechanism underlying them was investigated with DNA methyltransferase inhibitor (DNMT-i) . MS attenuated ADP differentiation into neuron. DNMT-i recovered MS-attenuated neural differentiation. MS decreased DNMT1 expression. These suggest that MS-increased DNA methylation might be involved in MS-attenuated ADP neural differentiation. Next, we focused on RARα as a candidate gene in which DNA methylation is altered by MS. MS decreased RARα expression. RARα agonist and antagonist reciprocally affected neural differentiation. DNMT-i recovered MS-decreased RARα expression. MS increased DNA methylation in RARαpromoter. Therefore, MS may attenuate ADP neural differentiation via increasing DNMT1 expression and DNA methylation in RARα promoter.
