Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression
Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression
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DOI：
10.1016/j.biopsych.2007.07.016
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发表时间：
2008-02-15
影响因子：
10.6
通讯作者：
Taylor, Jane R.
中科院分区：
文献类型：
--
作者：
Gourley, Shannon L.;Wu, Florence J.;Taylor, Jane R.
背景资料：海马中神经营养因子调节的转录因子（如环磷酸腺苷（cAMP）-反应元件结合蛋白（CREB））的磷酸化水平升高已被认为是在其他幼稚啮齿动物中抗抑郁药（ADT）疗效的常见介体。ADTs和糖皮质激素，抑郁症的因果因素，调节抑郁样行为的细胞内因素尚不清楚，但细胞外信号调节激酶1/2（ERK 1/2），CREB.Methods的上游，是一个可能的候选人：我们探讨了糖皮质激素暴露和随后的ADT治疗的长期后果在一个新的慢性抑郁症模型。动机的行为，不动在尾部悬挂，和ERK 1/2，已知需要的行为反应ADTs，进行了quantitatives.Results：慢性皮质酮（CORT）增加不动性，减少响应的操作性条件反射任务的动机，并选择性地减少磷酸化ERK 1/2（pERK 1/2）在齿状回。阿米替林（AMI）治疗后，行为和生化指标恢复至基线水平。皮质酮调节pERK 1/2的时间进程，其抑制与抑郁相关的热休克蛋白的增加和酪氨酸激酶受体B（trk B）磷酸化的降低。慢性AMI也产生了区域分离的影响，在CA 1/CA 3，杏仁核，纹状体，但不是前额叶cortic.Conclusions：Antibacterial功效的动机任务和行为绝望分析与改变边缘系统pERK 1/2，包括恢复pERK 1/2在齿状回应激相关的侮辱后。
Background: Elevated phosphorylation of neurotrophin-regulated transcription factors, such as cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), in the hippocampus has been proposed as a common mediator of antidepressant (ADT) efficacy in otherwise naive rodents. The intracellular factors by which ADTs and glucocorticoids, causal factors in depression, regulate depression-like behavior remain unclear, but extracellular signal-regulated kinase 1/2 (ERK1/2), upstream of CREB, is a likely candidate.Methods: We explored the long-term consequences of glucocorticoid exposure and subsequent ADT treatment in a novel model of chronic depression. Motivated behaviors, immobility during tail suspension, and ERK1/2, known to be required for behavioral response to ADTs, were quantified.Results: Chronic corticosterone (CORT) increased immobility, decreased responding in an operant conditioning task of motivation, and selectively reduced phosphorylated ERK1/2 (pERK1/2) in the dentate gyrus. Behavioral and biochemical measures were restored to baseline by amitriptyline (AMI) treatment. Corticosterone regulated pERK1/2 on a time course that paralleled increases in heat shock proteins associated with depression and decreased tyrosine kinase receptor B (trkB) phosphorylation. Chronic AMI also produced regionally dissociable effects on pERK1/2 in CA1/CA3, amygdala, and striatum, but not prefrontal cortex.Conclusions: Antidepressant efficacy in a motivational task and behavioral despair assay are associated with altered limbic pERK1/2, including restored pERK1/2 in the dentate gyrus after stress-related insult.