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 × 3 experimental design (MPTP ×± Mn) was as follows: SS, MPTP(-) × Mn(-); SLMn, MPTP(-) × low Mn(+); SHMn, MPTP(-) × high Mn(+); MpS, MPTP(+) × Mn(-); MpLMn, MPTP(+) × low Mn(+); MpHMn, MPTP(+) × 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.
Kim Y, Kim J, Ito K, Lim H-S, Cheong H-K, Kim JY, Shin YC, Kim KS, Moon Y.Idiopathic parkinsonism with superimposed manganese exposure: utility of positron emission tomography. Neurotoxicology1999; 20: 249–252.
2.
Kim Y, Kim JM, Kim J, Yoo C, Lee CR, Lee JH, Kim HK, Yang SO, Park J, Chung HK, Lee DS, Jeon B.Dopamine transporter density is decreased in parkinsonian patients with a history of manganese exposure; what does it mean?Mov Disord2002; 17: 568–575.
3.
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ. Occupational exposures to metals as risk factors for Parkinson's disease. Neurology1997; 48: 650–658.
4.
Gorell JM, Johnson CC, Rybicki BA, Peterson EL, Kortsha GX, Brown GG, Richardson RJ. Occupational exposures to manganese, copper, lead, iron, mercury and zinc and the risk of Parkinson's disease. Neurotoxicology1999; 20: 239–248.
5.
Zayed J, Ducic S, Campanella G, Panisset JC, Andre P, Masson H, Roy M.Environmental factors in the etiology of Parkinson's disease. Can J Neurol Sci1990; 17: 286–291.
6.
Semchuk KM, Love EJ, Lee LG. Parkinson's disease: a test of the multifactorial etiologic hypothesis. Neurology1993; 43: 1173–1180.
7.
Seidler A, Hellenbrand W, Robra B-P, Vieregge P, Nischan P, Joerg J, Oertel WH, Ulm G, Schneider E.Possible environmental, occupational, and other etiological factors for Parkinson's disease: a case control study in Germany. Neurology1996; 46: 1275–1284.
8.
Vieregge P, Heinzow B, Korf G, Teichert HM, Schleifenbaum P, Mosinger HU. Long-term exposure to manganese in rural well water has no neurological effects. Can J Neurol Sci1995; 22: 286–289.
9.
Park J, Yoo C-I, Sim CS, Kim J-W, Yi Y, Jung KY, Chung S-E, Kim Y.Occupations and Parkinson's disease: a case-control study in South Korea. Ind Health2004; 42: 352–358.
10.
Park J, Yoo C-I, Sim CS, Kim H, Kim JW, Jeon BS, Kim K-R, Bang O-Y, Lee W-Y, Yi Y, Jung KY, Chung S-E, Kim Y.Occupations and Parkinson's disease: a multicenter case-control study in South Korea. Neurotoxicology2005; 26: 99–105.
11.
Bonilla E, Prasad AL. Effects of chronic manganese intake on the levels of biogenic amines in rat brain regions. Neurobehav Toxicol Teratol1984; 6: 341–344.
12.
Autissier N, Rochette L, Dumas P, Beley A, Loireau A, Bralet J.Dopamine and norepinephrine turnover in various regions of the rat brain after chronic manganese chloride administration. Toxicology1982; 24: 175–182.
13.
Gianutsos G, Murray MT. Alterations in brain dopamine and GABA following inorganic or organic manganese administration. Neurotoxicology1982; 3: 75–81.
14.
Komura J, Sakamoto M.Effects of manganese forms on biogenic amines in the brain and behavioral alterations in the mouse - long-term oral administration of several manganese compounds. Environ Res1992; 57: 34–44.
15.
Yong VW, Perry TL, Godolphin WJ, Jones KA, Clavier RM, Ito M, Foulks JG. Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons. Neurotoxicology1986; 7: 19–24.
16.
Hong JS, Hung CR, Seth PK, Mason G, Bondy SC. Effect of manganese treatment on the levels of neurotransmitters, hormones, and neuropeptides: modulation by stress. Environ Res1984; 34: 242–249.
17.
Eriksson H, Lenngren S, Heilbronn E.Effect of longterm administration of manganese on biogenic amine levels in discrete striatal regions of rat brain. Arch Toxicol1987; 59: 426–431.
18.
Ali MM, Murthy RC, Mandal SK, Chandra SV. Effect of low protein diet on manganese neurotoxicity: III. Brain neurotransmitter levels. Neurobehav Toxicol Teratol1985; 7: 427–431.
19.
Chandra SV, Shukla GS. Concentrations of striatal catecholamines in rats given manganese chloride through drinking water. J Neurochem1981; 36: 683–687.
20.
Chandra SV, Shukla GS, Saxena DK. Manganeseinduced behavioral dysfunction and its neurochemical mechanism in growing mice. J Neurochem1979; 33: 1217–1221.
21.
Baek SY, Lee MJ, Jung HS, Kim HJ, Lee CR, Yoo C, Lee JH, Lee H, Yoon CS, Kim YH, Park J, Kim JW, Jeon BS, Kim Y.Effect of manganese exposure on MPTP neurotoxicities. NeuroToxicology2003; 24: 657–665.
22.
Barbeau A.Manganese and extrapyramidal disorders (a critical review and tribute to Dr George C Cotzias). Neurotoxicology1984; 5: 13–35.
23.
Calne DB, Chu NS, Huang CC, Lu CS, Olanow W.Manganism and idiopathic parkinsonism: similarities and differences. Neurology1994; 44: 1583–1586.
Racette BA, Antenor JA, McGee-Minnich L, Moerlein SM, Videen TO, Kotagal V, Perlmutter JS. [18F] FDOPA PET and clinical features in parkinsonism due to manganism. Mov Disord2005; 20: 492–496.
26.
Klos KJ, Ahlskog JE, Josephs KA, Fealey RD, Cowl CT, Kumar N.Neurologic spectrum of chronic liver failure and basal ganglia T1 hyperintensity on magnetic resonance imaging: probable manganese neurotoxicity. Arch Neurol2005; 62: 1385–1390.
27.
Franklin KBJ, Paxinos G.The mouse brain in stereotaxic coordinates, first edition. Academic Press, 1997.
German DC, Nelson EL, Liang CL, Speciale SG, Sinton CM, Sonsalla PK. The neurotoxin MPTP causes degeneration of specific nucleus A8, A9 and A10 dopaminergic neurons in the mouse. Neurodegeneration1996; 5: 299–312.
30.
Lee CS, Sauer H, Bjorklund A.Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by intrastriatal 6-hydroxydopamine in the rat. Neuroscience1996; 72: 641–653.
31.
Zigmond MJ, Abercrombie ED, Berger TW, Grace AA, Stricker EM. Compensations after lesions of central dopaminergic neurons some clinical and basic implications. Trends Neurosci1990; 13: 290–296.
32.
Shukla GS, Chandra SV. Manganese toxicity: lipid peroxidation in rat brain. Acta Pharmacol Toxicol1981; 48: 95–100.
33.
Scheuhammer AM, Cherian MG. Influence of chronic MnCl2 and EDTA treatment on tissue levels and urinary excretion of trace metals in rats. Arch Environ Contam Toxicol1982; 11: 515–520.
34.
Bull RJ. Paradoxical decrease in corpus striatal manganese concentrations with manganese load. Commun Psychopharmacol1978; 2: 17–20.
35.
Yamada M, Ohno S Okayasu I, Okeda R, Hatakeyama S, Watanabe H, Ushio K, Tsukagoshi H.Chronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brain. Acta Neuropathol1986; 70: 273–278.
36.
Shinotoh H, Snow BJ, Chu NS, Huang CC, Lu CS, Lee C, Takahashi H, Calne DB. Presynaptic and postsynaptic striatal dopaminergic function in patients with manganese intoxication: a positron emission tomography study. Neurology1997; 48: 1053–1055.
