Short-term manganese pretreatment partially protects against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces parkinsonism in human and non-human primates. Its mechanism of action is not fully elucidated. Recently, the participation of trace metals, such as manganese, on its neurotoxic action has been postulated. In this work, we studied the effect of manganese administration on the neurochemical consequences of MPTP neurotoxic action. Male Swiss albino mice were treated with manganese chloride (MnCl2.4H2O; 0.5 mg/ml or 1.0 mg/ml of drinking water) for 7 days, followed by three MPTP administrations (30 mg/kg, intraperitoneally). Seven days after the last MPTP administration, mice were sacrificed and dopamine and homovanillic acid contents in corpus striatum were analyzed. Striatal concentration of dopamine was found increased by 60% in mice pretreated with 0.5 mg/ml and 52% in the group treated of 1.0 mg/ml as compared versus animals treated with MPTP only. Homovanillic acid content in both groups treated with manganese was the same as those in control animals. The results indicate that manganese may interact with MPTP, producing an enhancement of striatal dopamine turnover, as the protective effect of manganese was more pronounced in the metabolite than in the neurotransmitter.
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Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, México.
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning; D008297:Male; D008345:Manganese / Q000627:therapeutic use*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*
D018696:Neuroprotective Agents; D008345:Manganese; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid