title: Corticosterone impairs hippocampal neuronal calcium regulation--possible mediating mechanisms.
abstract: Corticosterone (CORT), the predominant glucocorticoid of rats which is secreted during stress, increases hippocampal neuronal vulnerability to excitotoxins, hypoxia-ischemia, and hypoglycemia in an energy-dependent manner. A mechanism for this endangerment could be the CORT-induced impairment of hippocampal neuronal calcium regulation. We have shown that CORT causes an energy-dependent prolonged elevation of cytosolic free calcium ([Ca2+]i) in response to kainic acid stimulation in cultured hippocampal neurons. That study utilized the calcium-sensitive dye fluo-3, which is unsuitable for determination of basal [Ca2+]i. The present study circumvents that limitation by using the dye fura-2 AM. We have replicated the previous demonstration that CORT potentiates the [Ca2+]i response to KA; we have also observed that CORT elevates basal [Ca2+]i concentrations. Furthermore, we have observed that the mechanism for this CORT impairment of calcium regulation involves a reduction in stimulus-induced calcium efflux. Energy-dependent disruptions in neuronal calcium regulation, such as induced by CORT, have been associated with subsequent neurotoxicity. Thus, the CORT-induced impairment of hippocampal neuronal calcium regulation could be the mechanism for the neuronal vulnerability and toxicity evident following CORT treatment and stress.
authors.affiliation: Department of Biological Sciences, Stanford University, CA 94305.
authors.forename: E M
authors.initials: EM
authors.lastname: Elliott
authors.forename: R M
authors.initials: RM
authors.lastname: Sapolsky
mesh_terms: D000818:Animals; D001481:Basal Metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003345:Corticosterone / Q000502:physiology*; D016257:Fura-2; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002118:Calcium; D016257:Fura-2; D003345:Corticosterone