title: Blockade of metabotropic glutamate receptors inhibits cognition and neurodegeneration in an MPTP-induced Parkinson's disease rat model.
abstract: Hyperactivity of the glutamatergic system is involved in excitotoxicity and neurodegeneration in Parkinson's disease (PD). Metabotropic glutamate receptor subtype 5 (mGluR5) modulates glutamatergic transmission and thus has been proposed as a potential target for neuroprotective drugs. The aim of this study was to determine the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), an mGluR5 antagonist, on working memory, object recognition, and neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD rat model. Male Wistar rats were stereotaxically injected with MPTP into the substantia nigra pars compacta (SNc). Starting 1 day after lesioning (day 1), the rats were treated daily with MPEP (2mg/kg/day, i.p.) for 14 days and rats underwent a T-maze test on days 8-10 and an object recognition test on days 12-14. MPTP-lesioned rats showed impairments of working memory in the T-maze test and of recognition function in the object recognition test and both effects were prevented by MPEP treatment. Furthermore, MPTP lesion-induced dopaminergic degeneration in the nigrostriatal system, microglial activation in the SNc, and cell loss in the hippocampal CA1 area were all inhibited by MPEP treatment. These data provide support for a role of mGluR5s in the pathophysiology of PD and suggest that MPEP is a promising pharmacological tool for the development of new treatments for dementia associated with PD.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taiwan, ROC.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Hsieh
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Ho
authors.forename: Kuei-Ying
authors.initials: KY
authors.lastname: Yeh
authors.forename: Cornelius Rainer
authors.initials: CR
authors.lastname: Pawlak
authors.forename: Hung-Ming
authors.initials: HM
authors.lastname: Chang
authors.forename: Ying-Jui
authors.initials: YJ
authors.lastname: Ho
authors.forename: Te-Jen
authors.initials: TJ
authors.lastname: Lai
authors.forename: Fu-Ying
authors.initials: FY
authors.lastname: Wu
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D004195:Disease Models, Animal; D008297:Male; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000523:psychology; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; C121465:6-methyl-2-(phenylethynyl)pyridine