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首页> 外文期刊>The European Journal of Neuroscience >Changes in signaling pathways regulating neuroplasticity induced by neurokinin 1 receptor knockout.
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Changes in signaling pathways regulating neuroplasticity induced by neurokinin 1 receptor knockout.

机译：调节神经激肽1受体敲除诱导的神经可塑性的信号传导途径的变化。

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Abstract Neurokinin 1 (NK-1) receptor knockout mice showed behavioral responses similar to animals chronically treated with antidepressants. The aim of this study was to analyse, in NK-1 receptor knockout, the molecular modifications of signaling pathways involved in the pathophysiology of depression and antidepressant mechanism. We found, in total cell cytosol from the prefrontal/frontal cortex, hippocampus and striatum, a marked up-regulation of Ca(2+)-independent enzymatic activity and Thr(286) autophosphorylation of Ca(2+)/calmodulin-dependent protein kinase (CaMK) II. Similar changes in CaMKII regulation were previously observed in rats chronically treated with antidepressants. In striatum, up-regulation of the activity and phosphorylation of CaMKII was also found in the homogenate and synaptosomes. No major changes were observed in the Ca(2+)-dependent kinase activity, with the exception of homogenate from the prefrontal/frontal cortex. We also analysed the expression and phosphorylation of presynaptic proteins, which modulate synaptic vesicle trafficking and exocytosis, and found a marked decrease in synapsin I total expression and basal phosphorylation of Ser(603) (the phosphorylation site for CaMKII) in the prefrontal/frontal cortex. Accordingly, the Ca(2+)/calmodulin-dependent posthoc endogenous phosphorylation of synapsin I in the same area was increased. The knockout of NK-1 receptor had no consequences on the expression or phosphorylation levels of the transcription factor cAMP-responsive element-binding protein and its regulating kinase CaMKIV. However, phosphorylation of ERK1/2-mitogen-activated protein kinases was reduced in the hippocampus and striatum, again resembling an effect previously observed in antidepressant-treated rats. These results show similarities between NK-1 knockouts and animals chronically treated with antidepressants and support the putative antidepressant activity of NK-1 receptor antagonists.
机译：摘要神经激肽1（NK-1）敲除小鼠表现出与长期接受抗抑郁药治疗的动物相似的行为反应。这项研究的目的是在NK-1受体敲除中分析与抑郁症的病理生理和抗抑郁机制有关的信号通路的分子修饰。我们发现，在前额叶/额叶皮层，海马和纹状体的总细胞溶质中，Ca（2+）依赖性酶活性和Ca（2 +）/钙调蛋白依赖性蛋白的Thr（286）自磷酸化显着上调激酶（CaMK）II。先前在用抗抑郁药长期治疗的大鼠中观察到类似的CaMKII调节变化。在纹状体中，在匀浆和突触小体中也发现了CaMKII的活性和磷酸化的上调。没有重大变化的观察到Ca（2+）依赖激酶活性，从前额叶/额叶皮层匀浆除外。我们还分析了突触前蛋白的表达和磷酸化，可调节突触小泡的运输和胞吐作用，并发现前额叶/额叶皮层中突触素I的总表达和Ser（603）（CaMKII的磷酸化位点）的基础磷酸化显着降低。 。因此，在同一区域中突触素I的Ca（2 +）/钙调蛋白依赖性posthoc内源性磷酸化增加。 NK-1受体的敲除对转录因子cAMP响应元件结合蛋白及其调节激酶CaMKIV的表达或磷酸化水平没有影响。然而，海马和纹状体中ERK1 / 2-丝裂原活化蛋白激酶的磷酸化降低，再次类似于先前在抗抑郁药治疗的大鼠中观察到的效果。这些结果显示了NK-1基因敲除与长期接受抗抑郁药治疗的动物之间的相似性，并支持NK-1受体拮抗剂的假定抗抑郁活性。

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