Chiry Oriana, Fishbein William N, Merezhinskaya Natalya, Clarke Stéphanie, Galuske Ralf, Magistretti Pierre J, Pellerin Luc
Max Planck Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt am Main, Germany.
Brain Res. 2008 Aug 21;1226:61-9. doi: 10.1016/j.brainres.2008.06.025. Epub 2008 Jun 18.
The monocarboxylate transporter MCT2 belongs to a large family of membrane proteins involved in the transport of lactate, pyruvate and ketone bodies. Although its expression in rodent brain has been well documented, the presence of MCT2 in the human brain has been questioned on the basis of low mRNA abundance. In this study, the distribution of the monocarboxylate transporter MCT2 has been investigated in the cortex of normal adult human brain using an immunohistochemical approach. Widespread neuropil staining in all cortical layers was observed by light microscopy. Such a distribution was very similar in three different cortical areas investigated. At the cellular level, the expression of MCT2 could be observed in a large number of neurons, in fibers both in grey and white matter, as well as in some astrocytes, mostly localized in layer I and in the white matter. Double staining experiments combined with confocal microscopy confirmed the neuronal expression but also suggested a preferential postsynaptic localization of synaptic MCT2 expression. A few astrocytes in the grey matter appeared to exhibit MCT2 labelling but at low levels. Electron microscopy revealed strong MCT2 expression at asymmetric synapses in the postsynaptic density and also within the spine head but not in the presynaptic terminal. These data not only demonstrate neuronal MCT2 expression in human, but since a portion of it exhibits a distinct synaptic localization, it further supports a putative role for MCT2 in adjustment of energy supply to levels of activity.
单羧酸转运蛋白MCT2属于一个参与乳酸、丙酮酸和酮体转运的膜蛋白大家族。尽管其在啮齿动物脑中的表达已有充分记录,但基于低mRNA丰度,MCT2在人类脑中的存在受到了质疑。在本研究中,采用免疫组织化学方法研究了正常成人大脑皮质中单羧酸转运蛋白MCT2的分布。通过光学显微镜观察到所有皮质层均有广泛的神经纤维网染色。在三个不同的皮质区域进行研究,这种分布非常相似。在细胞水平上,MCT2的表达可在大量神经元、灰质和白质纤维以及一些星形胶质细胞中观察到,这些星形胶质细胞大多位于I层和白质中。结合共聚焦显微镜的双重染色实验证实了神经元表达,但也提示突触MCT2表达优先定位于突触后。灰质中的一些星形胶质细胞似乎有MCT2标记,但水平较低。电子显微镜显示,在突触后致密部的不对称突触以及棘突头部内有强烈的MCT2表达,但在突触前终末没有。这些数据不仅证明了人类神经元中MCT2的表达,而且由于其中一部分表现出独特的突触定位,进一步支持了MCT2在将能量供应调整到活动水平方面的假定作用。