Estrogens dynamically regulate neurogenesis in the dentate gyrus of adult female rats

Abstract

Estrone and estradiol differentially modulate neuroplasticity and cognition, but how they influence maturation pathways of new neurons in the adult hippocampus is not known. The present study assessed the effects of estrone and estradiol on various aspects of neurogenesis in the dentate gyrus (DG) of ovariectomized young adult Sprague-Dawley rats using daily subcutaneous injections of 17{beta}-estradiol or estrone. Rats were injected with a DNA synthesis marker, 5-bromo-2-deoxyuridine (BrdU), and were perfused one, two, or three weeks after BrdU injection and treatment. Immunofluorescent labelling for GFAP/Sox2 was used to examine the density of neural stem/progenitor cells and Ki67 for cell proliferation. Double-immunofluorescent labelling of BrdU with doublecortin (DCX) or NeuN was used to examine the attrition and maturation of adult-born neurons over time. Length of time post ovariectomy was associated with a reduction in neural stem/progenitor cells in the DG. Estrogens had effects on different components of neurogenesis after one week of exposure but not after prolonged treatment. Estradiol enhanced, whereas estrone reduced, cell proliferation after one week but not after longer exposure to hormones. Both estrogens increased the density of BrdU/DCX-ir cells after one week of exposure but showed greater attrition of new neurons between one and two weeks after exposure, suggesting that the effects of estrogens on neurogenesis were not sustained. These results demonstrate that estrogens modulate several aspects of adult hippocampal neurogenesis differently in the short term, but may lose their ability to influence neurogenesis after long-term exposure.