Simvastatin Prevents Dopaminergic Neurodegeneration in Experimental Parkinsonian Models The Association with Anti-Inflammatory Responses 英文参考文献.docVIP

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Simvastatin Prevents Dopaminergic Neurodegeneration in Experimental Parkinsonian Models The Association with Anti-Inflammatory Responses 英文参考文献.doc

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Simvastatin Prevents Dopaminergic Neurodegeneration in Experimental Parkinsonian Models The Association with Anti-Inflammatory Responses 英文参考文献

SimvastatinPreventsDopaminergicNeurodegeneration inExperimentalParkinsonianModels:TheAssociation withAnti-InflammatoryResponses JunqiangYan1.,YunqiXu1.,CanshengZhu1.,LiminZhang1,AiminWu1,YuYang1,ZhaojunXiong3, ChaoDeng2,Xu-FengHuang2,MidoriA.Yenari4,Yuan-GuoYang5,WeihaiYing5,QingWang1,2* 1Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China, 2Centre for Translational Neuroscience,SchoolofHealthSciences,UniversityofWollongong,NewSouthWales,Australia,3DepartmentofCardiology,TheThirdAffiliatedHospital,SunYat-Sen University, Guangzhou, People’s Republic of China, 4Department of Neurology, University of California San Francisco and the San Francisco Veterans Affairs Medical Center,SanFrancisco,California,UnitedStatesofAmerica,5Med-XResearchInstitute,ShanghaiJiaoTongUniversity,Shanghai,People’sRepublicofChina Abstract Background: In addition to their original applications to lowering cholesterol, statins display multiple neuroprotective effects.N-methyl-D-aspartate(NMDA)receptorsinteractcloselywiththedopaminergicsystemandarestronglyimplicated in therapeutic paradigms of Parkinson’s disease (PD). This study aims to investigate how simvastatin impacts on experimentalparkinsonianmodelsviaregulatingNMDAreceptors. Methodology/Principal Findings: Regional changes in NMDA receptors in the rat brain and anxiolytic-like activity were examinedafterunilateralmedialforebrainbundlelesionby6-hydroxydopamineviaa3-weekadministrationofsimvastatin. NMDA receptor alterations in the post-mortem rat brain were detected by [3H]MK-801(Dizocilpine) binding autoradiography. 6-hydroxydopamine treated PC12 was applied to investigate the neuroprotection of simvastatin, the associationwithNMDAreceptors,andtheanti-inflammation.6-hydroxydopamineinducedanxietyandthedownregulation ofNMDAreceptorsinthehippocampus,CA1(CornuAmmonis1Area),amygdalaandcaudateputamenwasobservedin6- OHDA(6-hydroxydopamine)lesionedratswhereassimva