CORTICOSTERONE IMPAIRS HIPPOCAMPAL NEURONAL CALCIUM REGULATION - POSSIBLE MEDIATING MECHANISMS

被引:137
作者
ELLIOTT, EM [1 ]
SAPOLSKY, RM [1 ]
机构
[1] STANFORD UNIV,DEPT BIOL SCI,STANFORD,CA 94305
关键词
CALCIUM; NEUROTOXICITY; CORTICOSTERONE; GLUCOCORTICOID; STRESS; HIPPOCAMPUS;
D O I
10.1016/0006-8993(93)90245-I
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:84 / 90
页数:7
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