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Blockade of NMDA receptor enhances corticosterone-induced downregulation of brain-derived neurotrophic factor gene expression in the rat hippocampus through cAMP response element binding protein pathway

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Author:
No author available
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
5
DOI:
10.3321/j.issn:0371-0874.2005.05.001
Key Word:
皮质酮;海马;脑源性神经营养因子;NMDA受体;MK801;cAMP反应元件结合蛋白

Abstract: 高浓度的皮质酮可引起海马形态与功能的损伤,其中脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的改变在海马形态与功能损伤中扮演重要角色.本实验的目的是观察单次皮下注射皮质酮后海马内BDNF mRNA、前体蛋白及成熟型蛋白表达的改变,并观察N-甲基-D-天冬氨酸(N-methyl-D-aspartate NMDA)受体阻滞剂MK801对皮质酮作用的影响.实验结果显示,单次皮下注射皮质酮2 mg/kg,3 h后海马内BDNF mRNA、前体蛋白及成熟型蛋白的表达均降低;MK801(0.1 mg/kg)对皮质酮的这一作用有增强效果.单独给予皮质酮或注射MK801 30 min后再给予皮质酮,均能明显降低海马中cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)的磷酸化水平,MK801与皮质酮联用时CREB的磷酸化水平降低更为显著(与单独给予皮质酮相比,P<0.05).实验结果提示,CREB磷酸化水平降低可能是皮质酮引起海马BDNF表达减少的重要中间环节,阻断NMDA受体可加强皮质酮降低BDNF表达的效应.

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