Altered regulation of CREB by chronic antidepressant administration in the brain of transgenic mice with impaired glucocorticoid receptor function
Altered regulation of CREB by chronic antidepressant administration in the brain of transgenic mice with impaired glucocorticoid receptor function
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DOI：
10.1016/s0893-133x(01)00401-8
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发表时间：
2002-05-01
影响因子：
7.6
通讯作者：
Brunello, N
中科院分区：
文献类型：
--
作者：
Blom, JMC;Tascedda, F;Brunello, N
抗抑郁药物对基因转录的各种影响已经被描述，并且已经提出改变基因表达是抑郁症的共同生物学基础。抗抑郁药的共同作用的一个靶点是对与cAMP级联相关的受体后途径和基因的调节的修饰作用。最近的研究表明，长期抗抑郁治疗导致环腺苷3 '，5'-单磷酸系统的持续激活和转录因子cAMP反应元件结合蛋白（CREB）的表达增加。采用糖皮质激素受体功能受损的抑郁症转基因动物模型，研究慢性抗抑郁治疗对不同脑区CREB表达的影响。野生型和转基因小鼠每天接受一次生理盐水、地昔帕明或氟西汀给药，持续21天。抗抑郁药对CREB mRNA的影响使用敏感的RNase保护测定进行分析。抗癫痫治疗导致CREB的神经解剖学和动物特异性表达模式。我们的研究结果表明，终身中枢糖皮质激素受体功能障碍的结果在一个改变的敏感性方面的影响，抗抑郁药的CREB的表达。(C)2002年美国神经精神药理学学会。出版社：Elsevier Science Inc.
Various effects of antidepressant drugs on gene transcription have been described and altered gene expression has been proposed as being a common biological basis underlying depressive illness. One target for the common action of antidepressants is a modifying effect on the regulation of postreceptor pathways and genes related to the cAMP cascade. Recent studies have demonstrated that long-term antidepressant treatment resulted in sustained activation of the cyclic adenosine 3',5'-monophosphate system and in increased expression of the transcription factor cAMP response element binding protein (CREB). A transgenic animal model of depression with impaired glucocorticoid receptor function was used to investigate the effect of chronic antidepressant treatments on CREB expression in different brain areas. Wild-type and transgenic mice received one administration of saline, desipramine, or fluoxetine, daily for 21 days. The effects of antidepressants on CREB mRNA were analyzed using a sensitive RNase protection assay. Antidepressant treatment resulted in a neuroanatomically and animal specific expression pattern of CREB. Our findings suggest that life-long central glucocorticoid receptor dysfunction results in an altered sensitivity with respect to the effects of antidepressants on the expression of CREB. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.