17beta-estradiol and predegenerated nerve graft effect on hippocampal neurogenesis in adult female rats.

OBJECTIVES: The aim of present work was to examine estrogen influence on neurogenesis in the model of predegenerated peripheral nerve grafts implantation into the rat hippocampal dentate gyrus.

METHODS: Experiment was carried out on female rats divided into three experimental groups: NO - non-ovariectomized, OV - ovariectomized and E - heterogeneous group with various 17-beta-estradiol substitution after ovariectomy. Proliferating cells were labeled with BrdU. Brains were subjected to immunohistochemical procedures to visualize nestin, GFAP and estrogen receptors (ERalpha and ERbeta).

RESULTS: Proliferation rate was highest in E groups with estrogen levels resembling that in proestrus phase. Ovariectomy resulted in higher than in NO group number of new neurons, while high hyperestrogenemia worsened the results. The proportions of nestin-labeled cells correlated in similar way with different hormonal state. We found also distinct co-localization of nestin and GFAP in E group (proestrus). It may suggest the presence of radial glia, a potential source of new neurons in adult mammals. Nerve graft induced ERalpha expression at the site of injury in all groups. Distribution of ERbeta in hippocampus was estradiol-dose-dependent and correlated with cell proliferation.

CONCLUSION: In our model, 17-beta-estradiol and predegenerated nerve graft implantation had synergistic effect on hippocampal neurogenesis.