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Abstract

New neurons continue to be generated in the adult dentate gyrus of the hippocampus. Corticosterone (CORT), a steroid secreted by the adrenal glands, had been shown to regulate progenitor proliferation. High levels of CORT suppress proliferation while low levels of the steroid stimulate it. Here we present an investigation into the regulation of survival by corticoids, with emphasis on the differential effects of the pre-mitotic and post-mitotic corticoid environments. Post-mitotic adrenalectomy increased subsequent survival of progenitors at 28 days, while additional CORT administered during the post-mitotic period decreased survival. In contrast, a corticoid-free environment prior to progenitor division resulted in a reduced survival rate of new cells and, similarly, high levels of CORT before proliferation reduced subsequent survival. In addition, phased treatment with CORT during a 27-day post-mitotic interval showed that newly formed cells lose their sensitivity to administered CORT after about 18 days. These results are the first to show that the corticoid environment both before and after cell division regulates survival.