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Manganese does not alter the severe neurotoxicity of MPTP

Department of Anatomy, Pusan National University Medical School, Busan, South Korea

Y H Kim

Department of Neuropsychiatry, School of Medicine and Paik Institute of Clinical Research, Inje University, Busan, South Korea

S O Oh

Department of Anatomy, Pusan National University Medical School, Busan, South Korea

C-R Lee

C I Yoo

J H Lee

H Lee

C S Sim

Department of Occupational and Environmental Medicine, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, South Korea

J Park

Occupational Safety and Health Research Institute, Incheon, South Korea

J-W Kim

Department of Neurology, Dong-A University School of Medicine, Busan, South Korea

C S Yoon

Department of Occupational Health, Catholic University of Daegu, Gyeongbuk, South Korea

Y Kim

Department of Occupational and Environmental Medicine, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan, South Korea

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 2 x 3 experimental design (MPTP x± Mn) was as follows: SS, MPTP(-) x Mn(-); SLMn, MPTP(-) x low Mn(+); SHMn, MPTP(-) x high Mn(+); MpS, MPTP(+) x Mn(-); MpLMn, MPTP(+) x low Mn(+); MpHMn, MPTP(+) x high 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 MnCl₂.4H₂O intraperitoneally, once a day for 3 weeks.

Blood and striatal Mn levels were elevated in the Mnexposed 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.

Key Words: manganese • MPTP • Parkinson disease • neurotoxicity • dopamine

Human & Experimental Toxicology, Vol. 26, No. 3, 203-211 (2007)
DOI: 10.1177/0960327107070567


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