NMDA ANTAGONISTS PARTIALLY PROTECT AGAINST MPTP INDUCED NEUROTOXICITY IN MICE

被引:86
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
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.
引用
收藏
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
    BEAL, MF
    [J]. ANNALS OF NEUROLOGY, 1992, 31 (02) : 119 - 130
  • [2] KYNURENINE PATHWAY MEASUREMENTS IN HUNTINGTONS-DISEASE STRIATUM - EVIDENCE FOR REDUCED FORMATION OF KYNURENIC ACID
    BEAL, MF
    MATSON, WR
    SWARTZ, KJ
    GAMACHE, PH
    BIRD, ED
    [J]. JOURNAL OF NEUROCHEMISTRY, 1990, 55 (04) : 1327 - 1339
  • [3] AMINOOXYACETIC ACID RESULTS IN EXCITOTOXIN LESIONS BY A NOVEL INDIRECT MECHANISM
    BEAL, MF
    SWARTZ, KJ
    HYMAN, BT
    STOREY, E
    FINN, SF
    KOROSHETZ, W
    [J]. JOURNAL OF NEUROCHEMISTRY, 1991, 57 (03) : 1068 - 1073
  • [4] THE MPTP MODEL - VERSATILE CONTRIBUTIONS TO THE TREATMENT OF IDIOPATHIC PARKINSONS-DISEASE
    BLOEM, BR
    IRWIN, I
    BURUMA, OJS
    HAAN, J
    ROOS, RAC
    TETRUD, JW
    LANGSTON, JW
    [J]. 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
    BROUILLET, E
    JENKINS, BG
    HYMAN, BT
    FERRANTE, RJ
    KOWALL, NW
    SRIVASTAVA, R
    ROY, DS
    ROSEN, BR
    BEAL, MF
    [J]. 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
    CHAN, P
    DELANNEY, LE
    IRWIN, I
    LANGSTON, JW
    DIMONTE, D
    [J]. 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
    CLEETER, MWJ
    COOPER, JM
    SCHAPIRA, AHV
    [J]. 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
    KUPSCH, A
    LOSCHMANN, PA
    SAUER, H
    ARNOLD, G
    RENNER, P
    PUFAL, D
    BURG, M
    WACHTEL, H
    TENBRUGGENCATE, G
    OERTEL, WH
    [J]. 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
    NICKLAS, WJ
    VYAS, I
    HEIKKILA, RE
    [J]. LIFE SCIENCES, 1985, 36 (26) : 2503 - 2508