Neurosurgery Research Group, Lausanne Hospital University (CHUV), Pavillon 3, 1011 Lausanne, Switzerland.
Neuroscience. 2010 Jun 2;167(4):1103-14. doi: 10.1016/j.neuroscience.2010.02.059. Epub 2010 Mar 10.
The presence of three water channels (aquaporins, AQP), AQP1, AQP4 and AQP9 were observed in normal brain and several rodent models of brain pathologies. Little is known about AQP distribution in the primate brain and its knowledge will be useful for future testing of drugs aimed at preventing brain edema formation. We studied the expression and cellular distribution of AQP1, 4 and 9 in the non-human primate brain. The distribution of AQP4 in the non-human primate brain was observed in perivascular astrocytes, comparable to the observation made in the rodent brain. In contrast with rodent, primate AQP1 is expressed in the processes and perivascular endfeet of a subtype of astrocytes mainly located in the white matter and the glia limitans, possibly involved in water homeostasis. AQP1 was also observed in neurons innervating the pial blood vessels, suggesting a possible role in cerebral blood flow regulation. As described in rodent, AQP9 mRNA and protein were detected in astrocytes and in catecholaminergic neurons. However additional locations were observed for AQP9 in populations of neurons located in several cortical areas of primate brains. This report describes a detailed study of AQP1, 4 and 9 distributions in the non-human primate brain, which adds to the data already published in rodent brains. This relevant species differences have to be considered carefully to assess potential drugs acting on AQPs non-human primate models before entering human clinical trials.
在正常脑和几种脑病理学的啮齿动物模型中观察到三种水通道(水通道蛋白,AQP),即 AQP1、AQP4 和 AQP9。关于灵长类动物脑内 AQP 的分布及其知识尚知之甚少,这对于未来测试旨在预防脑水肿形成的药物将是有用的。我们研究了非人类灵长类动物脑内 AQP1、4 和 9 的表达和细胞分布。在非人类灵长类动物脑内观察到 AQP4 分布在血管周星形胶质细胞中,与在啮齿动物脑内的观察结果相似。与啮齿动物不同,灵长类动物 AQP1 表达在主要位于白质和胶质界的星形胶质细胞的突起和血管周足中,可能参与水稳态。AQP1 也存在于支配软脑膜血管的神经元中,提示其可能在脑血流调节中发挥作用。与在啮齿动物中描述的一样,AQP9 mRNA 和蛋白在星形胶质细胞和儿茶酚胺能神经元中被检测到。然而,在灵长类动物脑内的几个皮质区的神经元群体中,还观察到了 AQP9 的其他位置。本报告详细描述了非人类灵长类动物脑内 AQP1、4 和 9 的分布,这增加了已在啮齿动物脑内发表的数据。在进入人类临床试验之前,必须仔细考虑这些相关的物种差异,以评估作用于非人类灵长类动物模型 AQP 的潜在药物。