Manganese does not alter the severe neurotoxicity of MPTP
2007
We utilized a mice model of Parkinsonism: (1) to evaluate 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity; and (2) to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. A 2x3 experimental design (MPTP x ±Mn) was as follows: SS, MPTP(-) xMn(-); SLMn, MPTP(-)xlow Mn(+); SHMn, MPTP(-)xhigh Mn(+); MpS, MPTP(+)xMn(-); MpLMn, MPTP(+) x low Mn(+); MpHMn, MPTP(+) xhigh Mn(+). We administered MPTP (30 mg/kg per day) to male C57BL/6 mice intraperitoneally, once a day for 5 days. Subsequently, mice were treated with either 2 or 8 mg/ kg of MnCl 2 . 4H 2 O intraperitoneally, once a day for 3 weeks. Blood and striatal Mn levels were elevated in the Mn-exposed groups. The number of tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta were decreased significantly in the MPTP-exposed groups. The densities of TH-ir axon terminals in caudate-putamen (CPU) were significantly decreased in the MPTP-treated groups. However, Mn treatment did not affect MPTP neurotoxicity. The densities of glial fibrillary acidic protein (GFAP)-ir astrocytes in the CPU or globus pallidus were significantly increased in the MPTP-treated groups. Concentrations of dopamine in the striatum were decreased significantly in the MPTP-exposed groups only, but Mn had no effect.
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