Ketanserin selectively blocks acute stress-induced changes in NGFI-A and mineralocorticoid receptor gene expression in hippocampal neurons

被引:18
作者
Olsson, T [1 ]
Hakansson, A [1 ]
Seckl, JR [1 ]
机构
[1] WESTERN GEN HOSP, DEPT MED, EDINBURGH EH4 2XU, MIDLOTHIAN, SCOTLAND
基金
英国惠康基金;
关键词
hippocampus; serotonin; steroid receptors; mineralocorticoid receptors; immediate-early genes; transcription factors;
D O I
10.1016/S0306-4522(96)00432-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Serotonin and glucocorticoids interact at the hippocampus to alter neuronal function. Serotonin and antidepressant drugs increase glucccorticoid receptor and mineralocorticoid receptor gene expression in hippocampal neurons over a few daps. The effects of serotonin are mediated via ketanserin-sensitive ''serotonin-2 type'' receptors and induction of cyclic A-MP, although the subsequent molecular mechanisms are unclear. Recently, we have shown that chronic environmental manipulations which induce glucocorticoid receptor gene expression in specific hippocampal subfields of the rat are associated with congruent induction of the transcription factor NGFI-A (zif268. krox24, egr-1) and repression of AP-2; both factors may bind to the glucocorticoid receptor gene promoter. However, any relationship between serotonin and these transcription factors is unknown. Here. we show that acute restraint stress, which causes serotonin release at the hippocampus, induces hipppocampal NGFI-A, but represses activator protein-2 and mineralocorticoid receptor gene expression within 90 min. These changes are sustained for 4 h, but not 12 h. Ketanserin attenuates the stress-induced rise in NGFI-A and fall in mineralocorticoid receptor gene expression, and partly also the fall in AP-2 messenger RNA expression. These data suggest that restraint stress, acting via serotonin release and ketanserin-sensitive serotonin receptors, produces rapid, transient and specific changes in transcription factor gene expression in hippocampal neurons. Any link between these effects and the control of glucocorticoid and mineralocorticoid receptor expression with chronic serotonin or antidepressant treatment remains to be elucidated. Copyright (C) 1996 IBRO.
引用
收藏
页码:441 / 448
页数:8
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