Time-course of hippocampal granule cell degeneration and changes in adult neurogenesis after adrenalectomy in rats

Abstract

The hippocampus maintains the remarkable ability to generate new neurons throughout the lifespan. Progenitor cells in the subgranular zone give rise mainly to granule cells that migrate to the granule cell layer and become mature, functionally integrated neurons. Numerous factors are capable of regulating the proliferation and survival of new neurons in the adult hippocampus. Corticosterone is one of the most potent factors. Stress results in a significant decrease in the number of dividing cells and exogenous corticosterone administration produces a similar result. Conversely, removal of circulating glucocorticoids via adrenalectomy has been shown to dramatically increase cell proliferation. However, no studies have examined the long-term effects of adrenalectomy on cell proliferation in the hippocampus. In addition to increasing cell proliferation in the hippocampus, chronic adrenalectomy induces ongoing cell death in the dentate gyrus. In order to determine the time course of cell proliferation and cell death in the dentate gyrus following corticosterone removal we examined the dentate gyrus of rats at several time points following adrenalectomy. We analyzed the number of proliferating cells based on Ki67 labeling and visualized cell death using Fluoro-Jade B. Here we show that although cell proliferation is initially enhanced by adrenalectomy, but the increase is transient; it is no longer apparent by 4 weeks after adrenalectomy. Furthermore, we demonstrate that cell death is pronounced by 3 days after adrenalectomy and continues for at least 23 weeks.