Further Evidences for Neuroprotective Effects of Melatonin

  • D. Franceschini
  • S. D. Skaper
  • M. Floreani
  • G. Borin
  • P. Giusti
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 467)

Abstract

The physiological roles of the pineal hormone melatonin are still not completely clarified. Recently it has been shown that melatonin is a potent, endogenous scavenger of reactive oxygen species suggesting that it might interfere with neurodegenerative processing involving free-radical formation and excitatory aminoacid release. These neuroprotective effects of melatonin may result, at least in part, from a sparing of glutathione reductase, which is decreased following administration of the neurotoxic agent kainate (KA) in rats. Moreover, KA causes a rapid decrease in glutathione (GSH) content of cultured cerebellar granule neurons but not in astrocytes. These cell types both express functional KA receptors, but only the former is sensitive to reactive oxygen species-dependent KA injury. Melatonin counteracts the changes in GSH, induced by KA, in cultured cerebellar granule neurons.

Keywords

Cerebellar Granule Cerebellar Granule Cell Cerebellar Granule Neuron Excitatory Amino Acid Receptor Cerebellar Granule Cell Culture 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Antolin, I., Rodriguez, C., Sainz, R.M., Mayo, J.C., Uria, H., Kotier, M.L., Rodriguez-Colunga, M.J., Tolivia, D., and Menendez-Pelaez, A., 1996, Neurohormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes, FASEB J. 10:882–890.PubMedGoogle Scholar
  2. Barlow-Walden, L.R., Reiter, R.J., Abe, M., Pablos, M.I., Menendez-Pelaez, A., Chen, L.-D., and Poeggeler, B., 1995, Melatonin stimulates brain glutathione peroxidase activity, Neurochem. Int. 26:497–502.PubMedCrossRefGoogle Scholar
  3. Bazan, N.G., Birckle, D.L., Tang, W., and Reddy, D.S., 1986, The accumulation of free arachidonic acid, diacylglycerols, prostaglandins, and lipoxygenase reaction products in the brain during experimental epilepsy, in: Basic Mechanisms of the Epilepsies (Advances in Neurology), Volume 44, (Delgado-Escueta, A.V., Ward, A.A., Woodbury, D.M., and Porter, R.J., eds.), Raven Press, New York.Google Scholar
  4. Bondy, S.C. and Lee, D.K., 1993, Oxidative stress induced by glutamate receptor agonists, Brain Res. 610:229–233.PubMedCrossRefGoogle Scholar
  5. Cagnoli, C.M., Atabay, C., Kharlamov, E., and Manev, H., 1995, Melatonin protects neurons from singlet oxygen-induced apoptosis, J. Pineal Res. 18:222–226.PubMedCrossRefGoogle Scholar
  6. Champney, T.H. and Champney, J.-A.C., 1992, Novel anticonvulsant action of chronic melatonin in the gerbil, Neuro Report 3:1152–1154.Google Scholar
  7. Cheng, Y. and Sun, A.Y., 1994, Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons, Neurochem. Res. 19:1557–1564.PubMedCrossRefGoogle Scholar
  8. Choi, D.W., 1988, Glutamate neurotoxicity and diseases of the nervous system, Neuron 1:623–634.PubMedCrossRefGoogle Scholar
  9. Chuang, J. and Lin, M.T., 1994, Pharmacological effects of melatonin treatment on both locomotor activity and brain serotonin release in rats, J. Pineal. Res. 17:11–16.PubMedCrossRefGoogle Scholar
  10. Cooper, A.J.L. and Meister, A., 1993, Glutathione in the brain: disorders of glutathione metabolism, in: The Molecular and Genetic Basis of Neurological Disease (Rosenberg, R., Prusiner, S., Di Mauro, S., Barchi, R., and Kunkel, L., eds.), Butterworths, Stoneham, Massachusetts.Google Scholar
  11. Coyle, J.T. and Puttfarcken, P., 1993, Oxidative stress, glutamate, and neu rodegenerative disorders, Science 262:689–695.PubMedCrossRefGoogle Scholar
  12. Dykens, J.A., Stern, A., and Trenkner, E., 1987, Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury, J. Neurochem. 49:1222–1228.PubMedCrossRefGoogle Scholar
  13. Floreani, M., Petrone, M., Debetto, P., and Palatini, P., 1997, A comparison between different methods for the determinations of reduced and oxidized glutathione in mammalian tissues, Free Radical Res. 26:449–455.CrossRefGoogle Scholar
  14. Giusti, P., Gusella, M., Lipartiti, M., Milani, D., Zhu, W., Vicini, S., and Manev, H., 1995, Melatonin protects primary cultures of cerebellar granule neurons from kainate but not from N-methyl-D-aspartate excitotoxicity, Exp. Neurol. 131:39–46.PubMedCrossRefGoogle Scholar
  15. Giusti, P., Franceschini, D., Petrone, M., Manev, H., and Floreani, M., 1996a, In vivo and in vitro protection against kainate-induced excitotoxicity by melatonin, J. Pineal. Res. 20:226–231.PubMedCrossRefGoogle Scholar
  16. Giusti, P., Lipartiti, M., Franceschini, D., Schiavo, N., Floreani, M., and Manev, H., 1996b, Neuroprotection by melatonin from kainate-induced excitotoxicity in rats, FASEB J. 10:891–896.PubMedGoogle Scholar
  17. Golombek, D.A., Martini, M., and Cardinali, D.P., 1993, Melatonin as an anxyolitic in rats: time dependence and interaction with the central GABAergic system, Eur. J. Pharmacol. 237:231–236.PubMedCrossRefGoogle Scholar
  18. Halliwell, B., 1992, Reactive oxygen species and the central nervous system, J. Neurochem. 59:1609–1623.PubMedCrossRefGoogle Scholar
  19. Huang, J. and Philbert, M.A., 1996, Cellular responses of cultured cerebellar astrocytes to ethacrynic acidinduced perturbation of subcellular glutathione homeostasis, Brain Res. 711:184–192.PubMedCrossRefGoogle Scholar
  20. Imlay, J.A. and Linn, S., 1988, DNA damage and oxygen radical toxicity, Science 240:1302–1309.PubMedCrossRefGoogle Scholar
  21. Jain, A., Mårtensson, J., Stole, E., Auld, P.A.M., and Meister, A., 1995, Glutathione deficiency leads to mito-chondrial damage in brain, Proc. Natl. Acad Sci. USA 88:1913–1917.CrossRefGoogle Scholar
  22. Kato, K., Puttfarchen, P.S., Lyons, E., and Coyle, J.T., 1991, Developmental time course and ionic dependence of kainate-mediated toxicity in rat cerebellar granule cell cultures, J. Pharmacol. Exp. Ther. 256:402–411.PubMedGoogle Scholar
  23. Le Bars, D., Thivolle, P., Vitte, P.A., Bojkowski, C., Chazot, G., Arendt, J., Frackowiak, R.S.J., and Claustrat, B., 1991, PET and plasma pharmacokinetic studies after bolus intravenous administration of [11C]mela-tonin in humans, Nucl. Med. Biol. 18:357–362.Google Scholar
  24. Manev, H., Kharlamov, A., and Armstrong, D.M., 1994, Photochemical brain injury in rats triggers DNA fragmentation, p53, and HS72, Neuroreport 5:2661–2664.PubMedCrossRefGoogle Scholar
  25. Manev, H., Cagnoli, C.M., Kharlamov, A., Atabay, C., and Kharlamov, E., 1995, In vitro and in vivo neuroprotection with melatonin against toxicity of singlet oxygen, Soc. Neurosci. Abstr. 21:1518.Google Scholar
  26. Manev, H., Uz, T., Kharlamov, A., and Joo J.Y., 1996, Increased brain damage after stroke or excitotoxic seizures in melatonin-deficient rats, Faseb J. 10:1546–1551.PubMedGoogle Scholar
  27. Marshall, K.A., Reiter, R.J., Poeggler, B., Aruoma, O., and Halliwell, B., 1996, Evaluation of the antioxida-tive activity of melatonin in vitro, Free Rad. Biol. Med. 21:307–3PubMedCrossRefGoogle Scholar
  28. Matuszak, Z., Reszka, K., Chignell, C.F., 1997, Reaction of melatonin and related indoles with hydroxyl radicals: EPR and spin trapping investigations, Free Rad. Biol. Med. 23:367–372.PubMedCrossRefGoogle Scholar
  29. McCaslin, P.P. and Morgan, W.W., 1987, Cultured cerebellar cells as an in vitro model of excitatory amino acid receptor function, Brain Res. 417:380–384.PubMedCrossRefGoogle Scholar
  30. Meister, A. and Anderson, M.E., 1983, Glutathione, Annu. Rev. Biochem. 52:711–760.PubMedCrossRefGoogle Scholar
  31. Melchiorri, D., Reiter, R.J., Sewerynek, E., Chen, L.D., and Nisticò, G., 1995, Melatonin reduces kainate-induced lipid peroxidation in homogenates of different brain regions, FASEB J. 9:1205–1210.PubMedGoogle Scholar
  32. Melchiorri, D., Reiter, R.J., Sewerynek, E., Hara, M., Chen, L.D., and Nisticò, G., 1996, Paraquat toxicity and oxidative damage: Reduction by melatonin, Biochem. Pharmacol. 51:1095–1099.PubMedCrossRefGoogle Scholar
  33. Menendez-Pelaez, A., Poeggeler, B., Reiter, R.J., Barlow-Walden, L.R., Pablos, M.I., and Tan, D.X., 1993, Nuclear localization of melatonin in different mammalian tissues: immunocytochemical and radioim-munoassay evidence, J. Cell. Biochem. 53:373–382.PubMedCrossRefGoogle Scholar
  34. Milani, D., Facci, L., Guidolin, D., Leon, A., and Skaper, S.D., 1989, Activation of polyphosphoinositide metabolism as a signal-transducing system coupled to excitatory amino acid receptors in astroglial cells, Glia 2:161–169.PubMedCrossRefGoogle Scholar
  35. Nicoletti, F., Wroblewski, J.T., Novelli, A., Alho, H., Guidotti, A., and Costa, E., 1986, The activation of inositol phospholipid metabolism as a signal-transducing system for excitatory amino acids in primary cultures of cerebellar granule cells, J. Neurosci. 6:1905–1911.PubMedGoogle Scholar
  36. Norlund, J.J. and Lerner, A.B., 1977, The effects of oral melatonin on skin color and on the release of pituitary hormones, J. Clin. Endocrinol. Metab. 45:768–775.CrossRefGoogle Scholar
  37. Olanow, C.W., 1992, An introduction to the free radical hypothesis in Parkinson’s disease, Ann. Neurol. 32:52–59.CrossRefGoogle Scholar
  38. Pellegrini-Giampietro, D.E., Cherici, E.G., Alesiani, M., Carla, V., Moroni, F., 1990, Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage, J. Neurosci. 10:1035–1041.PubMedGoogle Scholar
  39. Phillis, J.W., 1994, A “radical” view of cerebral ischemic injury, Prog. Neurobiol. 42:441–448.PubMedCrossRefGoogle Scholar
  40. Pieri, C., Marra, M., Moroni, F., Recchioni, R., and Marcheselli, F., 1994, Melatonin: A peroxyl radical message scavenger more effective than vitamine E, Life Sci. 55: PL271–PL276.PubMedCrossRefGoogle Scholar
  41. Pigeolet, E. and Remacle, J., 1991, Susceptibility of glutathione peroxidase to proteolysis after oxidative alterations by peroxides and hydroxyl radicals, Free Radical Biol. Med. 11:191–195.CrossRefGoogle Scholar
  42. Puttfarcken, P.S., Getz, and Coyle, J.T., 1993, Kainic acid-induced lipid peroxidation: protection with butylated hydroxytoluene and U78517F in primary cultures of cerebellar granule cells, Brain Res. 624:223–232.PubMedCrossRefGoogle Scholar
  43. Reiter, R.J., 1995, Oxidative processes and antioxidative defense mechanisms in the aging brain, FASEB J. 9:526–533.PubMedGoogle Scholar
  44. Reiter, R.J., Poeggeler, E., Tan, D.X., Chen, L.D., Manchester, L.C., and Guerrero, J.M., 1993, Antioxidant capacity of melatonin: A novel action not requiring receptors, Neuroendocrinol. Lett. 15:103–109.Google Scholar
  45. Romijn, H.J., 1978, The pineal, a tranquilizer organ?. Life Science, 23:2257–2273.CrossRefGoogle Scholar
  46. Saija, A., Princi, P., Pisani, A., Lanza, M., Scalese, M., Aramnejad, E., Cesarani, R., and Costa, G., 1997, Protective effect of glutathione on kainic acid-induced neuropathological changes in rat brain, Gen. Pharmacol. 25:97–102.Google Scholar
  47. Sewerynek, E., Melchiorri, D., Ortiz, G.G., Poeggeler, B., and Reiter, R.J., 1995, Melatonin reduces H2O2-induced lipid peroxidation in homogenates of different brain regions, J. Pineal Res. 19:51–56.PubMedCrossRefGoogle Scholar
  48. Sewerynek, E., Ortiz, G.G., Reiter, R.J., Pablos, M.I., Melchiorri, D., and Daniels, W.M., 1996, Lipopolysac-charide-induced DNA damage is greatly reduced in rats treated with the pineal hormone melatonin. Mol. Cell. Endocrinol. 117:183–188.PubMedCrossRefGoogle Scholar
  49. Sun, A.Y., Cheng, Y., Bu, Q., and Oldfield, F., 1992, The biochemical mechanisms of the excitotoxicity of kainic acid, Mol. Chem. Neuropathol. 17:51–63.PubMedCrossRefGoogle Scholar
  50. Tamarkin, L., Baird, C., and Almeida, O.F.X., 1985, Melatonin: A coordinating signal for mammalian reproduction?, Science 227:714–720.PubMedCrossRefGoogle Scholar
  51. Tan, D.Z., Chen, L.D., Poeggeler, B., Manchester, L.C., and Reiter, R.J., 1993, Melatonin: a potent, endogenous hydroxyl radical scavenger, Endocrine J. 1:57–60.Google Scholar
  52. Uz, T., Giusti, P., Franceschini, D., Kharlamov, A., and Manev, H., 1996, Protective effect of melatonin against hippocampal DNA damage induced by intraperitoneal administration of kainate to rats, Neuroscience 73:631–636.PubMedCrossRefGoogle Scholar
  53. Uz, T., Kharlamov, A., Joo, J.-Y., Franceschini, D., Giusti, P., and Manev, H., 1997, Kainate-induced DNA damage and p53 immunoreactivity in the rat hippocampus: protection with melatonin, Croatian Medical Journal 38:205–211.Google Scholar
  54. Wolff, S.P., Garner, A., Dean, R.T., 1986, Free radicals, lipids and protein degradation, Trends Biol. Sci. 11:27–31.CrossRefGoogle Scholar
  55. Wurtman, R.J., Axelrod, J., and Fisher, J.E., 1964, Melatonin synthesis in the pineal gland: Effect of the light mediated by sympathetic nervous system, Science, 143:1328–1329.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • D. Franceschini
    • 1
  • S. D. Skaper
    • 3
  • M. Floreani
    • 1
  • G. Borin
    • 2
  • P. Giusti
    • 1
  1. 1.Department of PharmacologyUniversity of PadovaPadovaItaly
  2. 2.Biopolymer Research Center CNR and Department of Organic ChemistryUniversity of PadovaPadovaItaly
  3. 3.Smith Kline Beecham Pharmaceuticals Neuroscience Research DepartmentHarlow, EssexUK

Personalised recommendations