Protective effect of melatonin in a chronic experimental model of Parkinson's disease.
Parkinson's disease is a chronic condition characterized by cell death of dopaminergic neurons mainly in the substantia nigra. Among the several experimental models used in mice for the study of Parkinson's disease 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced parkinsonism is perhaps the most commonly used. This neurotoxin has classically been applied acutely or sub-acutely to animals. In this paper we use a chronic experimental model for the study of Parkinson's disease where a low dose (15 mg/kg bw) of MPTP was administered during 35 days to mice to induce nigral cell death in a non-acute way thus emulating the chronic condition of the disease in humans. Free radical damage has been implicated in the origin of this degeneration. We found that the antioxidant melatonin (500 microg/kg bw) prevents cell death as well as the damage induced by chronic administration of MPTP measured as number of nigral cells, tyrosine hydroxylase levels, and several ultra-structural features. Melatonin, which easily passes the blood-brain barrier and lacks of any relevant side-effect, is proposed as a potential therapy agent to prevent the disease and/or its progression.
Antolín
Isaac
I
Departmento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, C/ Julían Clavería, 33006 Oviedo, Asturias, Spain.
Mayo
Juan Carlos
JC
Sainz
Rosa María
RM
del Brío
María de los Angeles
Mde L
Herrera
Federico
F
Martín
Vanesa
V
Rodríguez
Carmen
C
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D015388:Organelles / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D008550:Melatonin