title: Melatonin protects against neurobehavioral and mitochondrial deficits in a chronic mouse model of Parkinson's disease.
abstract: Neuronal oxidative stress and mitochondrial dysfunction have been implicated in Parkinson's disease. Melatonin is a natural antioxidant and free radical scavenger that has been shown to effectively reduce cellular oxidative stress and protect mitochondrial functions in vitro. However, whether melatonin is capable of slowing down the neurodegenerative process in animal models of Parkinson's disease remains controversial. In this research, we examined long-term melatonin treatment on striatal mitochondrial and dopaminergic functions and on animal locomotor performance in a chronic mouse model of Parkinson's disease originally established in our laboratory by gradually treating C57BL/6 mice with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (15 mg/kg, s.c.) and probenecid (250 mg/kg, i.p.) over five weeks. We report here that when the chronic Parkinsonian mice were pre-treated and continuously treated with melatonin (5mg/kg/day, i.p.) for 18 weeks, the defects of mitochondrial respiration, ATP and antioxidant enzyme levels detected in the striatum of chronic Parkinson's mice were fully preempted. Meanwhile, the striatal dopaminergic and locomotor deficits seen in the chronic Parkinson's mice were partially and significantly forestalled. These results imply that long-term melatonin is not only mitochondrial protective but also moderately neuronal protective in the chronic Parkinson's mice. Melatonin may potentially be effective for slowing down the progression of idiopathic Parkinson's disease and for reducing oxidative stress and respiratory chain inhibition in other mitochondrial disorders.
authors: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
authors: Gaurav
authors: G
authors: Patki
authors: Yuen-Sum
authors: YS
authors: Lau
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy / Q000523:psychology; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents; D010101:Oxygen Consumption / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology*; D004856:Postural Balance / Q000187:drug effects; D011339:Probenecid; D011597:Psychomotor Performance / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D000978:Antiparkinson Agents; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D014404:Tubulin; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D008550:Melatonin; D011339:Probenecid