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.

Changes in photoperiod alter Glut4 expression in skeletal muscle of C57BL/6J mice.

Seasonal changes in photoperiod influence body weight and metabolism in mice. Here, we examined the effect of changes in photoperiod on the expression of glucose transporter genes in the skeletal muscle and adipose tissue of C57BL/6J mice. Glut4 expression was lower in the gastrocnemius muscle of mice exposed to a short-duration day (SD) than those to a long-duration day (LD), with accompanying changes in GLUT4 protein levels. Although Glut4 expression in the mouse soleus muscle was higher under SD than under LD, GLUT4 protein levels remained unchanged. To confirm the functional significance of photoperiod-induced changes in Glut4 expression, we checked for variations in insulin sensitivity. Blood glucose levels after insulin injection remained high under SD, suggesting that the mice exposed to SD showed lower sensitivity to insulin than those exposed to LD. We also attempted to clarify the relationship between Glut4 expression and physical activity in the mice following changes in photoperiod. Locomotor activity, as detected via infrared beam sensor, was lower under SD than under LD. However, when we facilitated voluntary activity by using running wheels, the rotation of wheels was similar for both groups of mice. Although physical activity levels were enhanced due to running wheels, Glut4 expression in the gastrocnemius muscle remained unchanged. Thus, variations in photoperiod altered Glut4 expression in the mouse skeletal muscle, with subsequent changes in GLUT4 protein levels and insulin sensitivity; these effects might be independent of physical activity.

Exposure of C57BL/6J mice to long photoperiod during early life stages increases body weight and alters plasma metabolomic profiles in adulthood.

Perinatal photoperiod is an important regulator of physiological phenotype in adulthood. In this study, we demonstrated that postnatal (0-4 weeks old) exposure of C57BL/6J mice to long photoperiod induced persistent increase in body weight until adulthood, compared with the mice maintained under short photoperiod. The expression of peroxisome proliferator-activated receptor δ, a gene involved in fatty acid metabolism, was decreased in 10-week-old mice exposed to long photoperiod during 0-4 or 4-8 weeks of age. Plasma metabolomic profiles of adult mice exposed to a long photoperiod during the postnatal period (0-4 LD) were compared to those in the mice exposed to short photoperiod during the same period. Cluster analysis revealed that both carbon metabolic pathway and nucleic acid pathway were altered by the postnatal photoperiod. Levels of metabolites involved in glycolysis were significantly upregulated in 0-4 LD, suggesting that the mice in 0-4 LD use the glycolytic pathway for energy expenditure rather than the fatty acid oxidation pathway. In addition, the mice in 0-4 LD exhibited high levels of purine metabolites, which have a role in neuroprotection. In conclusion, postnatal exposure of C57BL/6J mice to long photoperiod induces increase in body weight and various changes in plasma metabolic profiles during adulthood.