Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor
Dynamic changes in AP-1 transcription factor DNA binding activity in rat brain following administration of antidepressant amitriptyline and brain-derived neurotrophic factor
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DOI：
10.1016/s0028-3908(03)00148-5
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发表时间：
2003-08-01
影响因子：
4.7
通讯作者：
Iyo, M
中科院分区：
文献类型：
--
作者：
Okamoto, H;Shino, Y;Iyo, M
本研究旨在检测抗抑郁药、阿米替林和脑源性神经营养因子 (BDNF) 对大鼠大脑中激活蛋白 1 (AP-1) DNA 结合活性的影响。急性给予阿米替林（5 或 10 mg/kg）最初会增加大鼠额叶皮层和海马中的 AP-1 DNA 结合活性，但随后会降低。长期服用阿米替林（5 或 10 mg/kg，每天一次，持续 3 周）最初会降低 AP-1 DNA 结合活性，但最终导致大鼠额叶皮层的 AP-1 DNA 结合活性持续升高。相反，长期服用阿米替林并不会影响海马中 AP-1 DNA 结合的低活性。然而，长期服用阿米替林（10 mg/kg，每天一次，持续 3 周）显着增加了海马体（增加 26.9%）和额叶皮层（增加 24.6%）的 BDNF 蛋白水平。直接将 BDNF（1 杯）注入海马齿状回可显着增加海马 AP-1 DNA 结合活性。这些结果表明AP-1转录因子可能受BDNF调节，并且它可能是抗抑郁药作用的重要靶点。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
The present study was undertaken to examine the effects of the antidepressant, amitriptyline, and brain-derived neurotrophic factor (BDNF) on activator protein-1 (AP-1) DNA binding activity in the rat brain. Acute administration of amitriptyline (5 or 10 mg/kg) initially increased but then decreased AP-1 DNA binding activity in the rat frontal cortex and hippocampus. Chronic administration of amitriptyline (5 or 10 mg/kg, once daily for 3 weeks) initially decreased AP-1 DNA binding activity but ultimately resulted in its persistent elevation in the rat frontal cortex. In contrast, the chronic administration of amitriptyline did not affect the low activity of AP-1 DNA binding in the hippocampus. However, chronic administration of amitriptyline (10 mg/kg, once daily for 3 weeks) significantly increased BDNF protein levels in the hippocampus (by 26.9%) and frontal cortex (by 24.6%). Direct infusion of BDNF (1 mug) into the hippocampal dentate gyrus significantly increased hippocampal AP-1 DNA binding activity. These results suggest that AP-1 transcription factor may be modulated by BDNF and that it may be an important target for the action of antidepressants. (C) 2003 Elsevier Science Ltd. All rights reserved.