Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson's disease

被引：61

作者：

Vernon, AC ^{[1
]}

Palmer, S ^{[1
]}

Datla, KP ^{[1
]}

Zbarsky, V ^{[1
]}

Croucher, MJ ^{[1
]}

Dexter, DT ^{[1
]}

机构：

[1] Charing Cross Hosp, Imperial Coll London, Fac Med, Dept Cellular & Mol Neurosci,Parkinsons Dis Res G, London W6 8RF, England

来源：

EUROPEAN JOURNAL OF NEUROSCIENCE | 2005年 / 22卷 / 07期

关键词：

6-hydroxydopamine; excitotoxicity; glutamate; metabotropic glutamate receptors; neuroprotection; Parkinson's disease;

D O I：

10.1111/j.1460-9568.2005.04362.x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Increasing evidence implicates glutamate-mediated excitotoxicity as a contributory factor in dopaminergic cell death in the substantia nigra pars compacta (SNc) in Parkinson's disease (PD). Previous studies have suggested that metabotropic glutamate receptor (mGluR) ligands are neuroprotective against excitotoxicity in vitro. In the present study, the neurotoxin 6-hydroxydopamine (6-OHDA) produced a significant loss (61.2 +/- 8.9%; P < 0.01) of tyrosine hydroxylase-immunopositive (TH+) cells in both the SNc and striatal dopamine (58.02 +/- 1.27%; P < 0.05) in control male Sprague-Dawley rats. Both losses were significantly attenuated by sub-chronic (7 day) treatment with the Group I mGluR antagonists, 2-methyl-6(phenylethynyl)-pyridine (MPEP) or (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385); the Group II mGluR agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC); or the Group III mGluR agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4). These data demonstrate a neuroprotective action of mGluR ligands in vivo against 6-OHDA toxicity that has important implications for the treatment of PD.

引用

页码：1799 / 1806

页数：8

共 45 条

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