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MPP+ selectively affects calcium homeostasis in mesencephalic cell cultures from embryonal C57/B16 mice

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Summary

1-Methyl-4-phenylpyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) serves as a valuable tool in animal models of Parkinson's disease. Primary cell cultures of mesencephalon from C57/B16 mice were used to investigate the effects of various dopaminergic neurotoxins on the intracellular calcium metabolism. MPP+ was compared to its precursor MPTP and a structural analogue paraquat (methylviologen). Direct addition of these neurotoxins (10 μM) to fura-2-labeled cells did not change intracellular calcium concentrations in the presence of 1 mM extracellular calcium. When mesencephalic neurons were exposed to the compounds for 24 hours, only MPP+ led to an increase in calcium concentration in the absence and presence of extracellular calcium (36%, p<0.05 and 47%, p<0.01 versus control group). Intracellular calcium concentrations in cortical cultures devoid of dopaminergic cells were not changed by the above neurotoxins. Thus MPP+ is shown to selectively increase intracellular calcium concentrations in mesencephalic cultures.

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References

  • Abe K, Kogure K (1987) Recovery from calcium-induced damage in a neuroblastoma cell line. Brain Res 423: 221–228

    Google Scholar 

  • Albano E, Bellomo G, Parola M, Carini R, Dianzani MU (1991) Stimulation of lipid peroxidation increases the intracellular calcium content of isolated hepatocytes. Biochim Biophys Acta 1091: 310–316

    Google Scholar 

  • Almers W, Neher E (1985) The Ca signal from fura-2 loaded mast cells depends strongly on the method of dye-loading. FEES 192(1): 13–18

    Google Scholar 

  • Barbeau A, Dallaire L, Buu NT, Poirier J, Rucinska E (1985) Comparative behavioral, biochemical and pigmentary effects of MPTP, MPP+ and paraquat in Rana Pipiens. Life Sci 37: 1529–1538

    Google Scholar 

  • Berger B, di Porzio U, Dagnet MC, Gay M, Vigny A, Glowinski J, Prochiantz A (1982) Long term development of mesencephalic dopaminergic neurons of mouse embryos in dissociated primary cultures: morphological and histochemical characteristics. Neuroscience 7: 193–205

    Google Scholar 

  • Bondy SC, McKee M (1990) Prevention of chemically induced synaptosomal changes. J Neurosci Res 25: 229–235

    Google Scholar 

  • Burns RS, Chiueh CC, Markey SP (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80: 4546–4550

    Google Scholar 

  • Chemeris NK, Iljin VI, Safronova VG (1988) Modulation of calcium current in snail neurons by dopamine: the role of intracellular free calcium. Brain Res 460: 142–145

    Google Scholar 

  • Choi DW (1988) Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. TINS 11(10): 465–469

    Google Scholar 

  • Comporti M (1989) Three models of free radical-induced cell injury. Chem Biol Interactions 72: 1–56

    Google Scholar 

  • Eckert R, Chad JE (1984) Inactivation of Ca channels. Proc Biophys Mol Biol 44: 215–267

    Google Scholar 

  • Engele J, Pilgrim C, Kirsch M, Reisert I (1989) Different developmental potentials of diencephalic and mesencephalic dopaminergic neurons in vitro. Brain Res 483: 98–109

    Google Scholar 

  • Farber JL (1981) The role of calcium in cell death. Life Sci 29: 1289–1295

    Google Scholar 

  • Friedman L, Mytilineou C (1987) The toxicity of MPTP to dopamine neurons in culture is reduced at high concentrations. Neurosci Lett 79: 65–72

    Google Scholar 

  • Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440–3450

    Google Scholar 

  • Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC (1984) Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 311: 467–469

    Google Scholar 

  • Heizmann CW, Braun K (1992) Changes in Ca2+-binding proteins in human neurodegenerative disorders. TINS 25(7): 259–264

    Google Scholar 

  • Huang H-M, Toral-Barza L, Gibson G (1991) Cytosolic free calcium and ATP in synaptosomes after ischemia. Life Sci 48(15): 1439–1445

    Google Scholar 

  • Koutsilieri E, Chan WW, Reinitzer D, Rausch W-D (1993) Functional changes in cocultures of mesencephalon and striatal neurons from embryonic C57/B16 mice due to low concentrations of 1-methyl-4-phenylpyridinium (MPP+). J Neural Transm 94: 189–197

    Google Scholar 

  • Lambert CE, Bondy SC (1989) Effects of MPTP, MPP+ and paraquat on mitochondrial potential and oxidative stress. Life Sci 44: 1277–1284

    Google Scholar 

  • Langston JW, Ballard PA (1984) Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Can J Neurol Sci 11: 160–166

    Google Scholar 

  • Larsson OM, Hertz L, Schousboe A (1986) Uptake of GABA and nipecotic acid in astrocytes and neurons in primary cultures: changes in the sodium coupling ratio during differentiation. J Neurosci Res 16: 699–708

    Google Scholar 

  • Larsson OM, Falch E, Krogsgaard-Larsen P, Schousboe A (1988) Kinetic characterization of inhibition of -aminobutyric acid uptake into cultured neurons and astrocytes by 4,4-diphenyl-3-butenyl derivatives of nipecotic acid and guavacine. J Neurochem 50: 818–823

    Google Scholar 

  • Liu J, Lauder JM (1991) Serotonin and nialamide differentially regulate survival and growth of cultured serotonin and catecholamine neurons. Dev Brain Res 60: 59–67

    Google Scholar 

  • Michel PP, Dandapani BK, Knusel B, Sanchez-Ramos J, Hefti F (1990a) Toxicity of 1-methyl-4-phenylpyridinium for rat dopaminergic neurons in culture: selectivity and irreversibility. J Neurochem 54(4): 1102–1109

    Google Scholar 

  • Michel PP, Bhuvaneshari K, Dandapani BK, Efange MN, Hefti F (1990b) Potential environment neurotoxins related to 1-methyl-4-phenylpyridinium: selective toxicity of 1-methyl-4-phenylpyridinium and 1-methyl-4-cyclohexylpyridinium for dopaminergic neurons in culture. Exp Neurol 108: 141–150

    Google Scholar 

  • Morris ME, Friedlich JJ, MacDonald JF (1987) Intracellular calcium in mammalian brain cells: fluorescence measurements with quin2. Exp Brain Res 65: 520–526

    Google Scholar 

  • Mytilineou C, Cohen G, Heikkila RE (1985) 1-Methyl-4-phenylpyridine (MPP+) is toxic to mesencephalic dopamine neurons in culture. Neurosci Lett 57: 19–24

    Google Scholar 

  • Orrenius S, Bellomo G (1986) Toxicological implications of perturbation of Ca2+ homeostasis in hepatocytes. In: Cheung WY (ed) Ca2+ and cell function. Plenum Press, New York London, pp 451–461

    Google Scholar 

  • Ramsey RR, Krueger MJ, Youngster SK, Gluck MR, Casida JE, Singer TP (1991) Interaction of 1-methyl-4-phenylpyridinium ion (MPP+) and its analogues with the rotenone/piericidin binding site of NADH dehydrogenase. J Neurochem 56: 1184–1190

    Google Scholar 

  • Rosenthal L, Zacchetti D, Madeddu L, Meldolesi J (1990) Mode of action of α-latrotoxin: role of divalent cations in Ca2+-dependent and Ca2+-independent effects mediated by the toxin. Mol Pharmacol 38: 917–923

    Google Scholar 

  • Schambra UB, Lauder JM, Silver J (1992) Atlas of the prenatal mouse brain. Academic Press, San Diego, pp 76–84, 108–112

    Google Scholar 

  • Sebben M, Gabrion J, Manzoni O, Sladeczek F, Gril C, Bockaert J, Dumuis A (1990) Establishment of a long-term primary culture of striatal neurons. Dev Brain Res 52: 229–239

    Google Scholar 

  • Sher E, Gotti C, Pandiella A, Madeddu L, Clementi E (1988) Intracellular calcium homeostasis in a human neuroblastoma cell line: modulation by depolarization, cholinergic receptors and α-latrotoxin. J Neurochem 50(6): 1708–1713

    Google Scholar 

  • Taglialatela M, Canzoniero LMT, Fatatis A, Di Renzo G, Yasumoto T, Annunziato L (1990) Effect of maitotoxin on cytosolic Ca2+ levels and membrane potential in purified rat brain synaptosomes. Biochim Biophys Acta 1026: 126–132

    Google Scholar 

  • Toyoda H, Rausch W-D, Inoue K, Ohno Y, Fujiyama Y, Takagi K, Saito Y (1991) Comparison of solanaceous glycoalkaloids-evoked Ca2+ influx in different types of cultured cells. Toxic in vitro 5(4): 347–351

    Google Scholar 

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  1. T. S. Chen

    Present address: Institute of Medical Chemistry, University of Veterinary Medicine, Vienna, Austria

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  1. Institute of Medical Chemistry, University of Veterinary Medicine, Vienna, Austria

    E. Koutsilieri & W. D. Rausch

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  2. E. Koutsilieri
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Chen, T.S., Koutsilieri, E. & Rausch, W.D. MPP+ selectively affects calcium homeostasis in mesencephalic cell cultures from embryonal C57/B16 mice. J. Neural Transmission 100, 153–163 (1995). https://doi.org/10.1007/BF01271538

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  • DOI: https://doi.org/10.1007/BF01271538

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