Van Liefferinge Joeri, Jensen Cathy J, Albertini Giulia, Bentea Eduard, Demuyser Thomas, Merckx Ellen, Aronica Eleonora, Smolders Ilse, Massie Ann
Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium.
Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium.
Neurosci Lett. 2015 Mar 17;590:184-8. doi: 10.1016/j.neulet.2015.01.080. Epub 2015 Feb 7.
Vesicular glutamate transporters (VGLUTs) are responsible for loading glutamate into synaptic vesicles. Altered VGLUT protein expression has been suggested to affect quantal size and glutamate release under both physiological and pathological conditions. In this study, we investigated mRNA and protein expression levels of the three VGLUT subtypes in hippocampal tissue of patients suffering from temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS), International League Against Epilepsy type 1 (ILAE type 1) compared to autopsy controls, using quantitative polymerase chain reaction and semi-quantitative western blotting. mRNA expression levels of the VGLUTs are unaffected in hippocampal epileptic tissue compared to autopsy controls. At the protein level, VGLUT1 expression remains unaltered, while VGLUT2 is significantly decreased and VGLUT3 protein is significantly increased in hippocampal biopsies from TLE patients compared to controls. Our findings at the protein level can be explained by previously described histopathological changes observed in HS. Although VGLUTs have been repeatedly investigated in distinct rodent epilepsy models, their expression levels were hitherto not fully unraveled in the most difficult-to-treat form of epilepsy: TLE with HS ILAE type 1. We here, demonstrate for the first time that VGLUT2 protein expression is significantly decreased and VGLUT3 protein is significantly increased in the hippocampus of patients suffering from TLE with HS ILAE type 1 compared to autopsy controls.
囊泡谷氨酸转运体（VGLUTs）负责将谷氨酸装载到突触小泡中。已有研究表明，在生理和病理条件下，VGLUT蛋白表达的改变会影响量子大小和谷氨酸释放。在本研究中，我们使用定量聚合酶链反应和半定量蛋白质印迹法，调查了患有伴海马硬化（HS）的颞叶癫痫（TLE）（国际抗癫痫联盟1型，ILAE 1型）患者海马组织中三种VGLUT亚型的mRNA和蛋白表达水平，并与尸检对照进行比较。与尸检对照相比，海马癫痫组织中VGLUTs的mRNA表达水平未受影响。在蛋白水平上，与对照组相比，TLE患者海马活检组织中VGLUT1表达未改变，而VGLUT2显著降低，VGLUT3蛋白显著增加。我们在蛋白水平上的发现可以用先前在HS中观察到的组织病理学变化来解释。尽管VGLUTs已在不同的啮齿动物癫痫模型中进行了反复研究，但在最难治疗的癫痫形式：伴HS ILAE 1型的TLE中，其表达水平迄今尚未完全阐明。我们在此首次证明，与尸检对照相比，患有伴HS ILAE 1型的TLE患者海马中VGLUT2蛋白表达显著降低，VGLUT3蛋白显著增加。
