Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus

Abstract

The dentate gyrus of the rat produces new granule neurons well into adulthood. In the adult, newly born granule neurons migrate from the hilus to the granule cell layer, receive synaptic input, extend axons into the mossy fiber pathway, and express a neuronal marker. No previous studies have identified factors that regulate neuronal birth in the adult dentate gyrus. In order to determine whether glucocorticoids control neurogenesis in the adult dentate gyrus, the effects of adrenal steroid manipulations on neuronal birth were assessed using [3H]thymidine autoradiography and immunohistochemistry for the neuronal marker neuron specific enolase. Acute treatment with corticosterone produced a significant decrease in the density of [3H]thymidine-labeled cells in the hilus of the dentate gyrus. In contrast, removal of endogenous adrenal steroids stimulated increased neuronal birth; adrenalectomy resulted in a significant increase in the number of neuron specific enolase-immunoreactive [3H]thymidine labeled cells in the granule cell layer compared to sham operation. Replacement of corticosterone to adrenalectomized rats after [3H]thymidine injection did not substantially alter the increase in neurogenesis observed following adrenalectomy, even though this replacement protects cells from adrenalectomy-induced cell death. These results indicate that the rate of neurogenesis in the dentate gyrus of the adult rat is dependent upon the levels of circulating adrenal steroids.