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.

Early-life Photoperiod Influences Depression-like Behavior, Prepulse Inhibition of the Acoustic Startle Response, and Hippocampal Astrogenesis in Mice.

Environmental factors during early life stages affect behavioral and physiological phenotypes in adulthood. We examined the effect of photoperiods during development on neurogenesis and affective behaviors during adolescence/adulthood using C57BL/6J mice. Mice were born and raised until weaning under long-day conditions (LDs) or short-day conditions (SDs), followed by a 12L12D cycle until adulthood. Adult mice born under SD showed a shorter latency to first immobility in the forced swim test when compared with the mice born under LD. The mice born under SD also exhibited significantly lower prepulse inhibition, which is a characteristic of schizophrenia. However, the mice exposed to SD and LD during the prenatal period only did not show differences in prepulse inhibition. At 4 weeks of age, there were less 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus (DG) of the hippocampus of mice born under SD when compared with mice born under LD. Double immunostaining showed that the mice born under SD showed less BrdU/glial fibrillary acidic protein (GFAP, an astrocyte marker) cells when compared with mice born under LD. Furthermore, expression of the glucocorticoid receptor in the DG was higher in mice born under SD, and the photoperiod-dependent changes in the number of BrdU-positive cells in the DG were abolished by administration of RU486, a glucocorticoid receptor antagonist. These results suggest that the photoperiod in early life alters astrogenesis in the hippocampus via the hypothalamic-pituitary-adrenal axis and may relate to affective behaviors in adulthood.