Adolescent Changes in Cellular Proliferation in the Dentate Gyrus of Male and Female C57BL/6N Mice Are Resilient to Chronic Oral Corticosterone Treatments

Ashna Shome, Razia Sultana, Alina Siddiqui, Russell D. Romeo

Adolescent development is marked by significant changes in neurobiological structure and function. One such change is the substantial adolescent-related decline in cellular proliferation and neurogenesis in the dentate gyrus of the hippocampal formation. Though the behavioral implications of these developmental shifts in cell proliferation are unclear, these changes might contribute to the altered cognitive and emotional functions associated with puberty and adolescence. The significant decrease in cellular proliferation throughout adolescence might make the hippocampus more vulnerable to perturbations during this developmental stage, particularly to factors known to disrupt neurogenesis, such as chronic exposure to stress-related hormones. To examine this possibility, we first measured cellular proliferation in the dentate gyrus of male and female C57BL/6N mice before and after adolescence and then assessed both cellular proliferation and the number of immature neurons in mice treated with oral corticosterone for 4 weeks during either adolescence or adulthood. We found significant age-related decreases in hippocampal cellular proliferation in both males and females. Though the greatest decrease in proliferation was during adolescence, we also observed that proliferation continued to decline through young adulthood. Despite the significant effect of chronic oral corticosterone on body weight gain in both the adolescent- and adult-treated males and females and the subtle, but significant suppressive effect of corticosterone on the number of immature neurons in the adolescent-treated males, cell proliferation in the hippocampus was unaffected by these treatments. These data show that the substantial adolescent-related change in cellular proliferation in the dentate gyrus is largely unaffected by chronic oral corticosterone exposure in males and females. Thus, despite being vulnerable to the metabolic effects of these chronic corticosterone treatments, these results indicate that the developmental changes in cellular proliferation in the dentate gyrus are relatively resilient to these treatments in mice.