NMDA ANTAGONISTS PARTIALLY PROTECT AGAINST MPTP INDUCED NEUROTOXICITY IN MICE

被引：87

作者：

BROUILLET, E

BEAL, MF

机构：

[1] MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114

[2] HARVARD UNIV,SCH MED,BOSTON,MA 02114

来源：

NEUROREPORT | 1993年 / 4卷 / 04期

关键词：

MPTP; MPP+; EXCITOTOXICITY; NMDA RECEPTORS; MK-801; CGP39551; LY274614; PARKINSONS DISEASE;

D O I：

10.1097/00001756-199304000-00011

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

RECENT studies show that N-methyl-D-aspartate (NMDA) antagonists protect against neurotoxicity induced by local injections of 1-methyl-4-phenylpyridinium (MPP+) in both the substantia nigra and the striatum. The present studies examined whether either systemic administration of the non-competitive NMDA antagonist MK-801 or the competitive NMDA antagonists CGP39551 and LY274614 would protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dopaminergic toxicity in mice. Administration of MK-801, CGP39551 or LY274614 for 24 hours partially but significantly attenuated striatal dopamine (DA) depletions induced by MPTP at both 24 h and 1 week. These results support the hypothesis that MPTP neurotoxicity involves a secondary excitotoxic mechanism mediated by NMDA receptors. Such a mechanism may play a role in the etiology of Parkinson's disease.

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页码：387 / 390

页数：4

相关论文

共 25 条

[1] DOES IMPAIRMENT OF ENERGY-METABOLISM RESULT IN EXCITOTOXIC NEURONAL DEATH IN NEURODEGENERATIVE ILLNESSES [J].

BEAL, MF .

ANNALS OF NEUROLOGY, 1992, 31 (02) :119-130

[2] KYNURENINE PATHWAY MEASUREMENTS IN HUNTINGTONS-DISEASE STRIATUM - EVIDENCE FOR REDUCED FORMATION OF KYNURENIC ACID [J].

BEAL, MF ;

MATSON, WR ;

SWARTZ, KJ ;

GAMACHE, PH ;

BIRD, ED .

JOURNAL OF NEUROCHEMISTRY, 1990, 55 (04) :1327-1339

[3] AMINOOXYACETIC ACID RESULTS IN EXCITOTOXIN LESIONS BY A NOVEL INDIRECT MECHANISM [J].

BEAL, MF ;

SWARTZ, KJ ;

HYMAN, BT ;

STOREY, E ;

FINN, SF ;

KOROSHETZ, W .

JOURNAL OF NEUROCHEMISTRY, 1991, 57 (03) :1068-1073

[4] THE MPTP MODEL - VERSATILE CONTRIBUTIONS TO THE TREATMENT OF IDIOPATHIC PARKINSONS-DISEASE [J].

BLOEM, BR ;

IRWIN, I ;

BURUMA, OJS ;

HAAN, J ;

ROOS, RAC ;

TETRUD, JW ;

LANGSTON, JW .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 1990, 97 (2-3) :273-293

[5] AGE-DEPENDENT VULNERABILITY OF THE STRIATUM TO THE MITOCHONDRIAL TOXIN 3-NITROPROPIONIC ACID [J].

BROUILLET, E ;

JENKINS, BG ;

HYMAN, BT ;

FERRANTE, RJ ;

KOWALL, NW ;

SRIVASTAVA, R ;

ROY, DS ;

ROSEN, BR ;

BEAL, MF .

JOURNAL OF NEUROCHEMISTRY, 1993, 60 (01) :356-359

[6] RAPID ATP LOSS CAUSED BY 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN MOUSE-BRAIN [J].

CHAN, P ;

DELANNEY, LE ;

IRWIN, I ;

LANGSTON, JW ;

DIMONTE, D .

JOURNAL OF NEUROCHEMISTRY, 1991, 57 (01) :348-351

[7] IRREVERSIBLE INHIBITION OF MITOCHONDRIAL COMPLEX-I BY 1-METHYL-4-PHENYLPYRIDINIUM - EVIDENCE FOR FREE-RADICAL INVOLVEMENT [J].

CLEETER, MWJ ;

COOPER, JM ;

SCHAPIRA, AHV .

JOURNAL OF NEUROCHEMISTRY, 1992, 58 (02) :786-789

[8]

HUCKER HB, 1983, DRUG METAB DISPOS, V11, P54

[9] DO NMDA RECEPTOR ANTAGONISTS PROTECT AGAINST MPTP-TOXICITY - BIOCHEMICAL AND IMMUNOCYTOCHEMICAL ANALYSES IN BLACK MICE [J].

KUPSCH, A ;

LOSCHMANN, PA ;

SAUER, H ;

ARNOLD, G ;

RENNER, P ;

PUFAL, D ;

BURG, M ;

WACHTEL, H ;

TENBRUGGENCATE, G ;

OERTEL, WH .

BRAIN RESEARCH, 1992, 592 (1-2) :74-83

[10] INHIBITION OF NADH-LINKED OXIDATION IN BRAIN MITOCHONDRIA BY 1-METHYL-4-PHENYL-PYRIDINE, A METABOLITE OF THE NEUROTOXIN, 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE [J].

NICKLAS, WJ ;

VYAS, I ;

HEIKKILA, RE .

LIFE SCIENCES, 1985, 36 (26) :2503-2508