Sex Differences and Similarities in Hippocampal Cellular Proliferation and the Number of Immature Neurons during Adolescence in Rats

Adolescence is associated with significant reductions in hippocampal cellular proliferation and neurogenesis, the physiological and behavioral implications of which are unclear. Though sex differences exist in these proliferative processes in adulthood, relatively little is known about the role sex plays in these adolescent-related changes. To address this gap, we examined cross-sectional area of the dentate gyrus and cellular proliferation, as measured by Ki-67 immunohistochemistry, in pre- (30 days), mid- (45 days), and post-adolescent (70 days) male and female rats. We also investigated the number of immature neurons using doublecortin (DCX) immunohistochemistry in pre- and post-adolescent males and females. Despite increases in the size of the dentate gyrus during adolescence, we found significant adolescent-related decreases in hippocampal proliferation in both males and females, with a more dramatic decrease in males, indicating both age- and sex-dependent changes in the dentate gyrus. We also found an adolescent-related decline in the number of immature neurons in the dentate gyrus of male rats and a female-biased sex difference in the number of immature neurons in adults. Given these significant changes in the dentate gyrus, these data suggest that this period in development might be particularly sensitive to internal and external factors known to modulate neurogenesis, with potential sex-specific neurobehavioral ramifications.