Sex and seasonal differences in the rate of cell proliferation in the dentate gyrus of adult wild meadow voles.

In order to study the neurobiological basis of seasonal changes in hippocampal structure and function, the rate of cell proliferation was examined in male and female wild meadow voles captured during different seasons. We found that the number of [3H]thymidine-labeled cells varied across the seasons and across sex in the meadow vole. Non-breeding female meadow voles had a higher rate of cell proliferation and cell death than males captured during either season or breeding females. These seasonal changes in the female meadow vole were associated with both fluctuating levels of adrenal steroids and gonadal steroids. Estradiol level was highly correlated with both the number of [3H]thymidine-labeled cells and the number of pyknotic cells in female meadow voles, with high levels of estradiol being associated with low levels of cell proliferation and cell death. Corticosterone level was associated with the number of [3H]thymidine-labeled cells in the hilus of female meadow voles. This seasonal change in the number of [3H]thymidine-labeled cells was also related to the overall volume of the hippocampus. At variance with past literature, there was no statistically significant sex difference favoring males in hippocampal volume, although the means were in the predicted direction. In male meadow voles, the number of pyknotic cells was related to testosterone level, with high levels of testosterone being associated with greater levels of cell death in the granular cell layer. There was also a suggestion that the number of [3H]thymidine-labeled cells in the hilus varied seasonally in males, with higher rates of cell proliferation during the breeding season than during the non-breeding season. In summary, we found that there were large fluctuations across the season in the rate of cell proliferation in the dentate gyrus of adult female meadow voles. Females captured during the non-breeding season had higher rates of cell proliferation in the granule cell layer than females captured during the breeding season. This seasonal fluctuation was related to hormone levels, with high levels of corticosterone and estradiol being related to lower levels of cell proliferation. These seasonal changes in cell proliferation may be related to known changes in spatial learning in the meadow vole and provide insights into changes in the hippocampus that occur in other species, including primates.