Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders

Neuroscience
L E HaynesI J Mitchell

Abstract

It has been shown previously that the synthetic corticosteroid dexamethasone induces apoptosis of granule cells in the dentate gyrus and striatopallidal neurons in the dorsomedial caudate-putamen. We investigated whether or not dexamethasone can induce damage to other neuronal populations. This issue was addressed using OX42 immunohistochemistry to visualise activated microglia and thereby gauge the extent of dexamethasone-induced neuronal death. A single dose of dexamethasone (20mg/kg, i.p.) administered to young male Sprague-Dawley rats induced a strong microglial reaction which was restricted to the striatum, the dentate gyrus and all of the CA subfields of the hippocampus. Some OX42-immunoreactive cells were also seen in the lateral septal nucleus. Subsequent quantitative analysis of silver/methenamine-stained sections confirmed that acute administration of dexamethasone induced apoptosis in the striatum and all regions of the hippocampus at doses as low as 0.7mg/kg. In contrast, dexamethasone failed to induce apoptosis in the lateral septal nucleus at doses up to 20mg/kg. The levels of dexamethasone-induced striatal and hippocampal apoptosis were attenuated by pretreatment with the corticosteroid receptor antagonist RU3848...Continue Reading

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