Chronic Exposure of Nicotine Modulates the Expressions of the Cerebellar Glial Glutamate Transporters in Rats

  • Lim, Dong-Koo (College of Pharmacy and Institute for Drug Development, Chonnam National University) ;
  • Kim, Han-Soo (College of Pharmacy and Institute for Drug Development, Chonnam National University)
  • Published : 2003.04.01

Abstract

Rats were given nicotine (25 ppm) in their drinking water at the start of their mating period in order to study the expressions of glutamate transporter subtypes in cerebellar astrocytes following the chronic exposure of nicotine after mating. After the offspring were delivered, each group was divided into two subgroups. One group, the control group, was given distilled water only and the other group, the experimental group, was given distilled water containing nicotine. The cerebellar astrocytes were prepared from 7 day-old pups at each group. Ten days after the cells were cultured, the expression of the glutamate transporter subtypes (GLAST and GLT-1) was determined using immunochemistry and immunoblotting. During the continuous treatments, the developmental expression patterns of the GLAST and GLT-1 in the cerebellum were also determined from 2, 4 and 8 week-old rats. The expression levels of GLAST in cultured astrocytes of both the pre- or post-natally exposed groups were higher than those of the control group. However, these expression levels of the continuously exposed group were lower than those of the control group. Compared to those of the control group, the GLT-1 expression levels of all the nicotine-treated groups were higher, particularly in the continuously treated group.. According to the results from the immochemistry procedure, the cerebellar GLAST and GLT-1 expression levels of all nicotine-treated groups were lower than those of the control group at each age. However, the immunoblotting procedure showed that the cerebellar GLT-1 expression levels of all the nicotine-treated groups were higher than those of the control group, except for the rats that were continuously exposed for 8 weeks using immunoblotting. These results suggest that the expression of the glial GLAST and GLT-1 are altered differently depending on the initial exposure time and the partcicular period of nicotine exposure. In addition, nicotine exposure during gestation has persistent effects on glial cells.

Keywords

References

  1. Ajarem, J. S. andAhmad, M., Prenatal nicotine exposure modifies behavior of mice through early development. Pharmacol. Biochem. Behav., 59, 313-318 (1993)
  2. Akaike, A., Tamura, Y, Yokota, T, Shimohama, S., and Kimura J., Nicotine-induced protection of cultured cortical neurons against N-methyl-O-aspartate receptor-mediated glutamate cytotoxicity. Brain Res., 644, 181-187 (1994) https://doi.org/10.1016/0006-8993(94)91678-0
  3. Aramakis, V. B. and Metherate, R., Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex. J. Neurosci., 18, 8485-8495 (1998)
  4. Arriza, J. L., Fairman, W. A., Wadiche, J. I., Murdoch, G. H., Kavanaugh, M. P., and Amara, S. G., Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. J. Neurosci., 14, 5559-5569 (1994)
  5. Birtwistle, J. and Hall K., Does nicotinehave beneficial effectsin the treatment of certain diseases? Br. J. Nurs., 5, 1195-1202 (1997)
  6. Borlongan, C. V., Shytle, R. D., Ross, S. D., Shimizu, T., Freeman, T. B., Cahill, D. W., and Sanberg, P. R., (-)-Nicotine protects against systemic kainic acid-induced excitotoxic effects. Exp. Neurology, 136, 261-265 (1995) https://doi.org/10.1006/exnr.1995.1103
  7. Bristol, L. A. and Rothstein, J. D., Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann. Neurol., 39, 676-679 (1996) https://doi.org/10.1002/ana.410390519
  8. Casado, M., Bendahan, A., Zafra, F., Danbolt, N. C., Aragon, C., Gimenez, C., and Kanner, B.I., Phosphorylation and modulation of brain glutamate transporters by protein kinase C. J. Biol. Chem., 268, 27313-27317 (1993)
  9. Colling ridge, G. L. and Lester R. A. J., Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol. Rev., 41,143-210 (1989)
  10. Conradt, M. and Stoffel, W., Inhibition of the high-affinity brain glutamate transporter GLAST via direct phosphorylation. J. Neurochem., 68, 1244-1251 (1997) https://doi.org/10.1046/j.1471-4159.1997.68031244.x
  11. Fairman, W. A., Vandenverg, R. J., Arriza, J. L., Kavanaugh, M. P., and Amara, S. G., An excitatory amino acid transporter with properties of a ligand-gated chloride channel. Nature, 375, 599-603 (1995) https://doi.org/10.1038/375599a0
  12. Fung, Y K., Schmid, M. J., Anderson, T. M., and Lau Y, Effects of nicotine withdrawal on central dopaminergic systems. Pharmacol. Biochem. Behav., 53, 635-640 (1996) https://doi.org/10.1016/0091-3057(95)02063-2
  13. Furuta, A., Rothstein, J. D., and Martin, L. J., Glutamate transporter protein subtypes are expressed differentially during rat CNS development. J. Neurosci., 17, 8363-8375 (1997)
  14. Garcia-Munoz, M., Patino, P, Young, S. J., and Groves P. M., Effects of nicotine on dopaminergic nigrostriatal axons requires stimulation of presynaptic glutamatergic receptors. J. Pharmacol. Exp. Ther., 277, 1685-1693 (1996)
  15. Gattu, M., Pauly, J. R., Boss, K. L., Summers, J. B., and Buccafusco J. J., Cognitive impairment in spontaneously hypertensive rats: role of central nicotinic receptors. Brain Res., 771, 89-103 (1997) https://doi.org/10.1016/S0006-8993(97)00793-2
  16. Gegelashvili, G. and Schousboe, A., High affinity glutamate transporters: Regulation of expression and activity. J. Pharmacol. Exp. Ther., 52, 6-15 (1997)
  17. Hazell, A. S., Rao, K. V. R., Danbolt, N. C., Pow, D. V., and Butterworth, R. F., Selective down-regulation of the astrocyte glutamate transporters GLT-1 and GLAST within the medial thalamus in experimental Wernickes encepholopathy. J. Neurochem., 78, 560-568 (2001) https://doi.org/10.1046/j.1471-4159.2001.00436.x
  18. Kondo, K., Hashimoto, H., Kitanaka, J., Sawada, M., Suzumura, A., Marunouchi, T., and Baba, A., Expression of glutamate transporters in cultured glial cells. Neurosci. Lett., 188, 140-142 (1995) https://doi.org/10.1016/0304-3940(95)11408-O
  19. Levy, L. M., Lehre, K. P, Walaas, S. I., Storm-Mathison, J., and Danbolt, N. C., Down-regulation of glial glutamate transporters after glutamatergic denervation in the rat brain. Eur. J. Neurosci., 7, 2036-2041 (1995) https://doi.org/10.1111/j.1460-9568.1995.tb00626.x
  20. Li, X., Zoli, M., Finnman, U., NeNovere, N., Changeux, J., and Fuxe, K., A single (-)-nicotine injection causes change with a time delay in the affinity of striatal $D_2$ receptors for antagonist, but not for agonist, nor in the $D_2$ receptor mRNA levels in the rat substantia nigra. Brain Res., 678, 157-167 (1995)
  21. Lim, D. K. and Kim H.S., Changes in the glutamate release and uptake of cerebellar cells in perinatally nicotine-exposed rat pups. Neurochem. Res., 26, 1119-1125 (2001) https://doi.org/10.1023/A:1012318805916
  22. Lim, D. K., Park, S. H., and Choi, W. J., Subacute nicotine D. K. Lim and H. S. Kim exposure in cultured cerebellar cells increased the release and uptake of glutamate. Arch. Pharm. Res., 23, 488-494 (2000) https://doi.org/10.1007/BF02976578
  23. LoPachin, R. M. and Aschner, M., Glial-neuronal interactions: Relevance to neurotoxic mechanisms. Toxicol. Appli. Pharmacol., 118, 141-158 (1993) https://doi.org/10.1006/taap.1993.1020
  24. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265-275 (1951)
  25. Martin, B. R., Nicotine receptors in the central nervous system. In Conn, P. M. (Ed), The receptors. Academic Press, New York, pp. 393-415 (1986)
  26. McCaslin, P P. and Morgan, W. W., Cultured cerebellar cells as in vitro model of excitatory amino acid receptor function. Brain Res., 417, 380-384 (1987) https://doi.org/10.1016/0006-8993(87)90469-0
  27. Meldrum, B. and Garthwaite, J., Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol. Sci., 11, 379-387 (1990) https://doi.org/10.1016/0165-6147(90)90184-A
  28. Mennerick, S. and Zorumski, C. F., Glial contribution to excitatory neurotransmission in cultured hippocampal cells. Nature, 368, 59-62 (1994) https://doi.org/10.1038/368059a0
  29. Nakayama, H., Numakawa, T., Ikeuchi, T., and Hatanaka, H., Nicotine-induced phosphorylation of extracellual signalregulated protein kinase and CREB in PC12h cells. J. Neurochem., 79, 489-498 (2001) https://doi.org/10.1046/j.1471-4159.2001.00602.x
  30. Newman, M. B., Shytle, R. D., and Sanberg, P. R., Locomotor behavioral effects of prenatal and postnatal nicotine exposure in rat offspring. Behav. Pharmacol., 10, 700-706 (1999)
  31. Nicholis, D. and Attwell, D., The release and uptake of excitatory amino acids. Trends Pharmacol. Sci., 11, 462-468 (1990) https://doi.org/10.1016/0165-6147(90)90129-V
  32. Nordberg, A., Zhang, X., Fredriksson, A., and Eriksson, P., Neonatal nicotine exposure induces permanent changes in brain nicotine receptors and behaviour in adult mice. Dev. Brain Res., 63, 201-207 (1991) https://doi.org/10.1016/0165-3806(91)90079-X
  33. Perez De La Mora, M., Mendez-Franco, J., Salceda, R., Aguirre, J. A., and Fuxe, K., Neurochemical effects of nicotine on glutamate and GABA mechanisms in the rat brain. Acta. Physiol. Scand., 141, 241-250 (1991) https://doi.org/10.1111/j.1748-1716.1991.tb09074.x
  34. Rao, V. L. R., Rao, A. M., Dogan, A., Bowen, K. K., Hatcher, J., Rothstein, J. D., and Demsey, R. J., Glial glutamate transporter GLT-1 down-regulation procedes delayed neuronal death in gerbril hippocampus following transient global cerebral ischemia. Neuchem. Int., 36, 531-537 (2000)
  35. Rop, P. P., Grimaldi, F., Oddoze, C., and Viala, A., Determination of nicotine and its main metabolites in urine by high performance liquid chromatography. J. Chromatogr., 612, 302-309 (1993) https://doi.org/10.1016/0378-4347(93)80177-6
  36. Roth, R. H., Elsworth, J. D., and Morrow, B. A., Prenatal nicotine exposure disrupts short-term memory in spontaneous object recognition task. Soc. Neurosci. Abs., 26, Part1, 1095 (2000)
  37. Rothstein, J. D., Dykes-Hoberg, M., Pardo, C. A., Bristol, L. A., Jin, L., Kuncl, R. W., Kanai, Y., Hediger, M., Wang, Y., Schinke, J. P., and Welty, D. F., Knockout of glutamate transporters reveals a major role for astroglia transport in exctotoxicity and clearance of glutamate. Neuron, 16, 675-686 (1996) https://doi.org/10.1016/S0896-6273(00)80086-0
  38. Seal, R P. and Amara, S. G., Excitatory amino acid transporters: A farnity in flux. Annu. Rev. Pharmacol. Toxicol., 39, 431-456 (1993) https://doi.org/10.1146/annurev.pharmtox.39.1.431
  39. Sutheland, M. L., Delaney, T. A., and Noebel, J. L., Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS. J. Neurosci., 16, 2191-2207 (1996)
  40. Swanson, R. A., Liu, J., Miller, J. M., Rothstein, J. D., Farrell, K., Stein, E,. A., and Longuemare, M. C., Neuronal regulation of glutemate transporter subtype expression in astrocytes. J. Neurosci., 17, 932-940 (1997)
  41. Tang, B., Hanna, S. T., and wang, R., Effects of nicotine on $K^{+}$ channel currents in vascular smooth muscle cells rat tail arteies, Eur. J. Pharmacol., 364, 247-254 (1999) https://doi.org/10.1016/S0014-2999(98)00833-4
  42. Thomas, J. D., Garrison, M. E., Slawecki, C. J., Ehlers, C. L., and Riley, E. P., Nicotine exposure during the neonatal brain growth spurt produces hyperactivity in preweanling rats. Neurotoxicol. Teratol., 22, 695-701 (2000) https://doi.org/10.1016/S0892-0362(00)00096-9
  43. Tizabi, Y, Russell, L. T, Nespor, S. M., Perry, D. C., and Grunberg, N. E., Prenatal nicotine exposure: Effects on locomotor activity and central [$^{125}I$]$\alpha$-BT binding in rats. Pharmacol. Biochem. Behav., 66, 495-500 (2000) https://doi.org/10.1016/S0091-3057(00)00171-4
  44. Trotti, D., Rizzini, B. L., Rossi, D., Haugeto, O., Racagni, G., Danbolt, N. C., and Volterra, A., Neuronal and glial glutamate transporters possess an SH-based redox regulatory mechanism. Eur. J. Neurosci., 9, 1236-1243 (1997) https://doi.org/10.1111/j.1460-9568.1997.tb01478.x
  45. Tzavara, E. T, Monory, K., Hanoune, J., and Nomikos, G. G., Nicotine withdrawal syndrome: behabioural distress and selective up-regulation of the cyclic AMP pathway in the amygdala. Eur. J. Neurosci., 16, 149-153 (2002) https://doi.org/10.1046/j.1460-9568.2002.02061.x
  46. Zhang, X., Gong, Z., and Nordberg, A, Effects of chronic treatment with (+)- and (-)-nicotine on nicotinic acetylcholine receptors and N-methyl-D-aspartate receptors in rat brain. Brain Res., 644, 32-39 (1994) https://doi.org/10.1016/0006-8993(94)90343-3