Creatine and Cyclocreatine Attenuate MPTP Neurotoxicity
| Autor: | Rima Kaddurah-Daouk, Russell T. Matthews, Autumn M. Klein, Gerald Mueller, Lichuan Yang, M. Flint Beal, Péter Klivényi, Robert J. Ferrante |
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| Rok vydání: | 1999 |
| Předmět: |
Male
1-Methyl-4-phenylpyridinium medicine.medical_specialty Tyrosine 3-Monooxygenase Dopamine Dopamine Agents Administration Oral Substantia nigra Creatine Phosphocreatine Mice chemistry.chemical_compound Developmental Neuroscience Internal medicine medicine Animals Neurotoxin Neurons biology Tyrosine hydroxylase business.industry MPTP MPTP Poisoning Immunohistochemistry nervous system diseases Substantia Nigra Neuroprotective Agents Endocrinology nervous system Neurology chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Creatinine Nissl Bodies biology.protein Creatine kinase business |
| Zdroj: | Experimental Neurology. 157:142-149 |
| ISSN: | 0014-4886 |
| DOI: | 10.1006/exnr.1999.7049 |
| Popis: | Systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPP+), which blocks complex I of the electron transport chain. Oral supplementation with creatine or cyclocreatine, which are substrates for creatine kinase, may increase phosphocreatine (PCr) or cyclophosphocreatine (PCCr) and buffer against ATP depletion and thereby exert neuroprotective effects. In the present study we found that oral supplementation with either creatine or cyclocreatine produced significant protection against MPTP-induced dopamine depletions in mice. Creatine protected against MPTP-induced loss of Nissl and tyrosine hydroxylase immunostained neurons in the substantia nigra. Creatine and cyclocreatine had no effects on the conversion of MPTP to MPP+ in vivo. These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability for Parkinson's disease. |
| Databáze: | OpenAIRE |
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