Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain
Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain
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DOI：
10.1046/j.1471-4159.2002.00809.x
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发表时间：
2002-04-01
影响因子：
4.7
通讯作者：
Parsadaniantz, SM
中科院分区：
文献类型：
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作者：
Banisadr, G;Quéraud-Lesaux, F;Parsadaniantz, SM
最近的研究表明，趋化因子单核细胞趋化蛋白-1（MCP-1）/CCL2及其受体CCR2在多种脑部疾病中发挥重要作用。在本研究中，我们利用定量放射自显影技术，研究了大鼠脑中[I-125]MCP-1/CCL2结合的药理学特性，清楚地显示了CCR2受体在大脑皮层、伏隔核、纹状体、杏仁核、丘脑、下丘脑、海马、黑质、乳头体和中缝核中的分布。此外，使用双荧光免疫组织化学，我们发现 CCR2 受体在神经元和星形胶质细胞上持续表达。使用 RT-PCR 方法，我们证明 CCR2 mRNA 存在于上述各个大脑区域中。急性腹腔内注射脂多糖四小时后，我们发现MCP-1/CCL2结合在多个脑结构中上调；这种效应发生在 CCR2B 标记的神经元和星形胶质细胞上，并且在较小程度上发生在激活的小胶质细胞上。为了探索 CCR2 的神经生物学功能，进行了活动测定研究。脑室内注射 MCP-1/CCL2 后，我们发现运动活动明显下降。我们的研究结果为大脑中具有精确神经解剖学和细胞定位的组成型 CCR2 受体表达及其在炎症过程中的调节提供了第一个证据，表明 MCP-1/CCL2 和 CCR2 在 CNS 中发挥重要的生理和病理生理作用。
Recent studies demonstrated that the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 and its receptor, CCR2, play important roles in various brain diseases. In this study, using quantitative autoradiography, we studied the pharmacological properties of [I-125]MCP-1/CCL2 binding in rat brain and we clearly showed the distribution of CCR2 receptors in cerebral cortex, nucleus accumbens, striatum, amygdala, thalamus, hypothalamus, hippocampus, substantia nigra, mammillary bodies and raphe nuclei. Moreover, using double fluorescent immunohistochemistry, we showed that CCR2 receptors were constitutively expressed on neurons and astrocytes. Using RT-PCR methods, we demonstrated that CCR2 mRNA is present in various brain areas described above. Four hours after an acute intraperitoneal lipopolysaccharide injection, we showed that MCP-1/CCL2 binding was up-regulated in several brain structures; this effect took place on both CCR2B labelled neurons and astrocytes and to a lesser extent on activated microglia. To explore neurobiological function of CCR2, actimetric study was carried out. After intracerebroventricular injections of MCP-1/CCL2, we showed that motor activity was markedly decreased. Our results provide the first evidence for constitutive CCR2 receptor expression with precise neuroanatomical and cellular localizations in the brain, and its regulation during an inflammatory process, suggesting that MCP-1/CCL2 and CCR2 play important physiological and pathophysiological role(s) in the CNS.