亲代谢型谷氨酸受体与帕金森病的相关性研究

本课题从行为学、病理学、生化学等多层次并结合PET、微透析等技术整体、动态地研究亲恍凸劝彼崾芴逵肱两鹕〉南喙匦裕⑻剿餮≡裥郧状恍凸劝彼崾芴寮ざ梁娃卓辜炼耘两鹕∧Ｐ椭⒆囱У母纳谱饔眉岸耘两鹕》⑸⒎⒄构痰挠跋臁１狙芯康慕峁唤瞿茉诶砺凵咸岢雠两鹕〉牟∫蜓卵担椅兄菩碌闹瘟埔┪锾峁├硐氲陌斜辍?..

Glutamate is the main excitatory amino acid (EAA) in the central nervous system. Metabotropic glutamate receptors ( mGluRs) belong to the G protein-coupled receptors family. It is still unknown whether mGluRs are involved in the pathogenesis and progress of Parkinson's disease. In the carrying out of the present project, the relation of mGluRs and the pathogenesis of PD was investigated systematically with putative animal and cell models using behavioral, pathological and biochemical methods, as well as microdialysis combined with high performance liquid chromatography (HPLC) assay. Our results demonstrated that Group I mGluR agonist DHPG and antagonist AP3 had no effect on 6-OHDA and MPP+-induced apoptosis of PC12 cell line and rat astrocytes. Group II mGluRs agonist DCGIV suppressed 6-OHDA and MPP+-induced apoptosis of rat astrocytes, but lacked of effect on PC12 cells. DCGIV and KATP opener IPT decreased 6-OHDA and MPP+-induced glutamate release significantly. Both 6-OHDA and MPP+ reduced the activity of glutamate transporters (GluT) in PC12 cells and rat glia cells concentration-dependently, which could be reversed by Group II mGluRs agonist DCGIV. Microdialysis studies found that Group II and III mGluRs agonists elevated extracellular dopamine and glutamate levels in the striatum of PD rat. Immunohistochemistry studies revealed that expression of Group II and III mGluRs increased dramatically in the cerebral cortex, striatum and hippocampus of PD rat. Our findings suggest that mGluRs are related to the pathogenesis and progress of Parkinson's disease. These studies shed light on the etiological and therapeutical research of PD, and provide a useful target for the development of new drugs in PD therapy.