Effect of postnatal photoperiod on DNA methylation dynamics in the mouse brain.

Season of birth influences the onset of psychiatric diseases in mammals. Recent studies using rodent models have revealed that photoperiod during early life stages has a strong impact on affective and cognitive behaviors, neuronal activity, and hippocampal neurogenesis/astrogenesis in later life. The present study examined the effect of postnatal photoperiod on global DNA methylation and hydroxymethylation dynamics in the mouse brain. Male mice born under short-day (SD) conditions were divided into SD and long-day (LD) groups on the day of birth. Temporal expression of DNA methyltransferases (DNMT1/3a) with 5-methylcytosine (5-mC) levels, as well as protein levels of ten-eleven translocation (TET) 2 with 5-hydroxymethylcytosine (5-hmC) levels, were analyzed from postnatal day 4 (P4) to P21. Levels of 5-hmC in all hippocampal areas were higher in the LD group than in the SD group at P21, with a positive correlation between 5-hmC levels and TET2 levels throughout the experimental period. Inconsistent results were observed between DNMT1/3a mRNA levels and 5-mC levels. On the other hand, in the OB, mRNA levels of DNMT1 and DNMT3a were slightly lower in the LD group similar to 5-mC levels, but TET2 and 5-hmC levels were not influenced by the photoperiod. In conclusion, postnatal exposure of mice to LD conditions induces an increase in TET2-dependent DNA hydroxymethylation in the hippocampus, which might be involved in the long-term effects of postnatal photoperiod on neurogenesis and affective/cognitive behaviors.