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.
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