Deprivation of mother–pup interaction by early weaning alters myelin formation in male, but not female, ICR mice

We previously reported that early-weaned Balb/c mice develop a persistent increase in anxiety as well as aggression, and we suggested that deprivation of mother–pup interaction from postnatal days 15 to 21 might account for this phenomenon. In the present study, we investigated developmental changes in myelin formation and behavioral effects of early weaning in male and female ICR mice. Early weaning was associated with decreased numbers of open-arm entries in an elevated plus-maze for both male and female mice at 3 weeks of age (W3); this effect was persistently observed in males, but ceased after W3 in females. Compared to the brains of normally weaned mice, the brains of the early-weaned males at W8 and of the females at W5 were of lesser mass. Western blotting with whole-brain homogenates identified four isoforms of myelin basic protein (MBP; 21.5, 18.5, 17.0, and 14.0 kDa). Expression of these MBPs increased gradually in normally weaned mice. In contrast, in the early-weaned male mice, but not the early-weaned female mice, it increased robustly at W3 and then declined at W5, as compared to the normally weaned mice. These results suggest that early weaning influences not only anxiety-related behavior but also myelin formation in the brain during the developmental period, particularly between 3 and 5 weeks of age, and male mice are more vulnerable than females to early-weaning effects on behavior and myelin formation.