Department of Psychiatry, Douglas Mental Health University Institute, McGill University Montreal, QC, Canada.
Institut National de la Santé et de la Recherche Médicale, UMR-S 1130, Neuroscience Paris Seine Paris, France ; Centre National de la Recherche Scientifique UMR 8246, Neuroscience Paris Seine Paris, France ; Sorbonne University, Université Pierre et Marie Curie Paris 06, UM119, Neuroscience Paris Seine Paris, France.
Front Neuroanat. 2015 Mar 5;9:23. doi: 10.3389/fnana.2015.00023. eCollection 2015.
Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3) are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe) while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.
谷氨酸是大脑中主要的兴奋性递质。囊泡谷氨酸转运体 (VGLUT1-3) 负责将谷氨酸装入突触小泡。VGLUT1 和 VGLUT2 被认为是经典谷氨酸能神经元的特异性标志物，而 VGLUT3 则存在于先前被认为使用除谷氨酸以外的其他神经递质的神经元中。尽管在啮齿动物大脑中这些谷氨酸能标志物的定位有丰富的文献，但目前对人类大脑中 VGLUT1-3 的分布知之甚少。在本研究中，我们使用亚型特异性探针和抗血清，通过原位杂交、免疫放射自显影和免疫组织化学技术，研究了三种囊泡谷氨酸转运体在人脑中的定位。我们发现 VGLUT1 转录本在大脑皮层、海马体和小脑高度表达，而 VGLUT2 mRNA 主要在丘脑和脑干中发现。VGLUT3 mRNA 定位于大脑皮层、海马体、纹状体和中缝核内的少量神经元中。免疫放射自显影标记后，在所有研究区域（大脑皮层、海马体、尾壳核、小脑、丘脑、杏仁核、黑质、中缝核）都观察到强烈的 VGLUT1 和 VGLUT2 免疫反应性，而 VGLUT3 则不存在于丘脑和小脑。人类大脑中 VGLUT1-3 的广泛定位揭示了其分布与啮齿动物大脑中描述的分布大部分对应。
