Corticosterone increases damage and cytosolic calcium accumulation associated with ethanol withdrawal in rat hippocampal slice cultures.
Corticosterone increases damage and cytosolic calcium accumulation associated with ethanol withdrawal in rat hippocampal slice cultures.
复制标题
皮质酮增加大鼠海马切片培养物中与乙醇戒断相关的损伤和胞质钙积累。
DOI：
10.1097/01.alc.0000163509.27577.da
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Prendergast,MarkA
中科院分区：
文献类型：
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作者：
Mulholland,PatrickJ;Self,RachelL;Harris,BartonR;Little,HilaryJ;Littleton,JohnM;Prendergast,MarkA
BackgroundEvidence suggests that stress hormones (i.e., glucocorticoids) may be increased during acute or chronic consumption of ethanol and during withdrawal from ethanol consumption, effects that may contribute to the development of cognitive impairment. The goal of the current studies was to examine the hypothesis that increased glucocorticoid levels in conjunction with ethanol exposure and withdrawal may cause hippocampal damage.MethodsOrganotypic hippocampal slice cultures were exposed to 50 mM ethanol for 10 days and withdrawn for 1 day. After withdrawal, cytotoxicity and cytosolic Ca2+accumulation were measured using the nucleic acid stain propidium iodide and Calcium Orange, AM, respectively. Cultures were also treated with nontoxic concentrations of corticosterone (0.001–1 μM) during ethanol exposure and withdrawal or only during withdrawal. Additional cultures were coexposed to corticosterone and RU486 (0.1–10.0 μM), spironolactone (0.1–10.0 μM), or MK‐801 (20 μM) during ethanol exposure and/or withdrawal.ResultsEthanol withdrawal did not increase propidium iodide fluorescence and cytosolic Ca2+levels. However, significant increases in propidium iodide fluorescence and in cytosolic Ca2+accumulation were observed in cultures when corticosterone (≥ 100 nM) was exposed during ethanol treatment and/or withdrawal. These effects of corticosterone on ethanol withdrawal were attenuated by RU486 and MK‐801 but not by spironolactone coexposure.ConclusionsThis report demonstrated that corticosterone exposure during ethanol treatment and/or withdrawal resulted in significant hippocampal damage, possibly via activation of glucocorticoid receptors and enhancement of the glutamatergic cascade. The findings from these studies suggest that glucocorticoids contribute to the neuropathological consequences of alcohol dependence in humans.
