P. Rojas et C. Rios, SHORT-TERM MANGANESE PRETREATMENT PARTIALLY PROTECTS AGAINST 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE NEUROTOXICITY, Neurochemical research, 20(10), 1995, pp. 1217-1223
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP) is a neurotoxin that
induces parkinsonism in human and non-human primates. Its mechanism o
f action is not fully elucidated. Recently, the participation of trace
metals, such as manganese, on its neurotoxic action has been postulat
ed. 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 . 4H(2)O; 0.5
mg/ml or 1.0 mg/ml of drinking water) for 7 days, followed by three MP
TP administrations (30 mg/Kg, intraperitoneally). Seven days after the
last MPTP administration, mice were sacrificed and dopamine and homov
anillic acid contents in corpus striatum were analyzed. Striatal conce
ntration of dopamine was found increased by 60% in mice pretreated wit
h 0.5 mg/ml and 52% in the group treated of 1.0 mg/ml as compared vers
us animals treated with MPTP only. Homovanillic acid content in both g
roups 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 neurot
ransmitter.