Carozzi Valentina Alda, Canta Annalisa, Oggioni Norberto, Ceresa Cecilia, Marmiroli Paola, Konvalinka Jan, Zoia Chiara, Bossi Mario, Ferrarese Carlo, Tredici Giovanni, Cavaletti Guido
Department of Neurosciences and Biomedical Technologies, University of Milano-Bicocca, Monza (MI), Italy.
J Anat. 2008 Nov;213(5):539-46. doi: 10.1111/j.1469-7580.2008.00984.x.
l-Glutamate is one of the major excitatory neurotransmitters in the mammalian central nervous system, but recently it has been shown to have a role also in the transduction of sensory input at the periphery, and in particular in the nociceptive pathway. An excess of glutamate is implicated in cases of peripheral neuropathies as well. Conventional therapeutic approaches for treating these diseases have focused on blocking glutamate receptors with small molecules or on reducing its synthesis of the receptors through the inhibition of glutamate carboxypeptidase II (GCPII), the enzyme that generates glutamate. In vivo studies have demonstrated that the pharmacological inhibition of GCPII can either prevent or treat the peripheral nerve changes in both BB/Wor and chemically induced diabetes in rats. In this study, we characterized the expression and distribution of glutamate transporters GLT1, GLAST, EAAC1 and of the enzyme GCPII in the peripheral nervous system of female Wistar rats. Immunoblotting results demonstrated that all glutamate transporters and GCPII are present in dorsal root ganglia (DRG) and the sciatic nerve. Immunofluorescence localization studies revealed that both DRG and sciatic nerves were immunopositive for all glutamate transporters and for GCPII. In DRG, satellite cells were positive for GLT1 and GCPII, whereas sensory neurons were positive for EAAC1. GLAST was localized in both neurons and satellite cells. In the sciatic nerve, GLT1 and GCPII were expressed in the cytoplasm of Schwann cells, whereas GLAST and EAAC1 stained the myelin layer. Our results give for the first time a complete characterization of the glutamate transporter system in the peripheral nervous system. Therefore, they are important both for understanding glutamatergic signalling in the PNS and for establishing new strategies to treat peripheral neuropathies.
L-谷氨酸是哺乳动物中枢神经系统中的主要兴奋性神经递质之一，但最近研究表明它在外周感觉输入转导中也发挥作用，尤其是在伤害感受通路中。外周神经病变病例中也存在谷氨酸过量的情况。治疗这些疾病的传统方法主要集中在使用小分子阻断谷氨酸受体，或通过抑制生成谷氨酸的谷氨酸羧肽酶II（GCPII）来减少受体的合成。体内研究表明，对GCPII的药理抑制可以预防或治疗大鼠BB/Wor和化学诱导糖尿病中的外周神经变化。在本研究中，我们对雌性Wistar大鼠外周神经系统中谷氨酸转运体GLT1、GLAST、EAAC1以及酶GCPII的表达和分布进行了表征。免疫印迹结果表明，所有谷氨酸转运体和GCPII均存在于背根神经节（DRG）和坐骨神经中。免疫荧光定位研究显示，DRG和坐骨神经对所有谷氨酸转运体和GCPII均呈免疫阳性。在DRG中，卫星细胞对GLT1和GCPII呈阳性，而感觉神经元对EAAC1呈阳性。GLAST定位于神经元和卫星细胞中。在坐骨神经中，GLT1和GCPII在雪旺细胞的细胞质中表达，而GLAST和EAAC1则对髓鞘层进行染色。我们的结果首次对外周神经系统中的谷氨酸转运体系统进行了完整表征。因此，它们对于理解外周神经系统中的谷氨酸能信号传导以及建立治疗外周神经病变的新策略都很重要。
