Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
J Neurochem. 2010 Apr;113(2):543-51. doi: 10.1111/j.1471-4159.2010.06623.x. Epub 2010 Jan 28.
While it is accepted that noradrenaline (NA) reduction in brain contributes to the progression of certain neurodegenerative diseases, the mechanisms through which NA exerts its protective actions are not well known. We previously reported that NA induced production of monocyte chemoattractant protein (MCP-1/CCL2) in cultured astrocytes mediated some of the neuroprotective actions of NA. We have now examined the regulation of MCP-1 production in vivo. Treatment of mice with the NA precursor l-threo-3,4-dihydroxyphenylserine induced the production of MCP-1 in astrocytes. In contrast, exposure to stress (a process known to elevate brain NA levels) produced only a moderate increase of MCP-1 because of the inhibitory activity of glucocorticoids released during the stress response. Similarly, corticosterone treatment of astrocytes caused a reduction of constitutive as well as the NA-induced MCP-1 production. When stressed rats had the production of glucocorticoids blocked by the selective inhibitor metyrapone, a large increase of MCP-1 concentration was observed in cortex, whereas propranolol (a beta adrenergic receptor blocker) avoided modifications of MCP-1 after stress. Desipramine (an inhibitor of NA reuptake) also caused an increase of MCP-1 in cortex. These data suggest that some phenomena caused by the alteration of NA or glucocorticoids could be mediated by MCP-1.
虽然人们普遍认为，大脑中去甲肾上腺素（NA）的减少会导致某些神经退行性疾病的进展，但 NA 发挥其保护作用的机制尚不清楚。我们之前曾报道过，NA 诱导培养的星形胶质细胞中单核细胞趋化蛋白-1（MCP-1/CCL2）的产生，介导了 NA 的部分神经保护作用。我们现在已经研究了 MCP-1 产生的体内调节。用 NA 前体 l-苏-3,4-二羟基苯丙氨酸处理小鼠会诱导星形胶质细胞中 MCP-1 的产生。相比之下，应激暴露（已知会升高大脑 NA 水平的过程）只会引起 MCP-1 的适度增加，因为应激反应中释放的糖皮质激素具有抑制作用。同样，皮质酮处理星形胶质细胞会导致组成性和 NA 诱导的 MCP-1 产生减少。当应激大鼠的糖皮质激素生成被选择性抑制剂甲吡酮阻断时，皮质中 MCP-1 浓度会大幅增加，而普萘洛尔（β肾上腺素能受体阻滞剂）可避免应激后 MCP-1 的改变。去甲丙咪嗪（NA 再摄取抑制剂）也会导致皮质中 MCP-1 增加。这些数据表明，NA 或糖皮质激素改变引起的一些现象可能是由 MCP-1 介导的。
