Taurine 2 pp 507-517 | Cite as

Balanced Interaction of Growth Factors and Taurine Regulate Energy Metabolism, Neuronal Survival, and Function of Cultured Mouse Cerebellar Cells under Depolarizing Conditions

  • E. Trenkner
  • A. El Idrissi
  • C. Harris
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 403)


The development of neuronal cells in a given cellular environment requires mechanisms that dynamically regulate the balanced interactions of multiple factors which are known to control maintenance and plasticity in function of neurons throughout constantly changing extracellular conditions. Periodic release of excitatory amino acids from both developing glial and neuronal cells into the extracellular environment and their uptake has been shown to stimulate neuronal function in concert with growth factors that control the degree of depolarization and, therefore, neuronal function. This study attempts to characterize the critical concentrations of these factors either alone or together in relation to energy metabolism, cell survival and function. We demonstrate a close correlation between energy metabolism of neuronal cells, controlled by the combination of growth-factors (βFGF, BDNF), and glutamate-taurine as well as K+ in depolarizing concentrations (10–25 mM), during the balancing act of neuronal survival or death, and neuronal function. These functions depend on medium conditions (energy sources, ion composition), the ratio of glial cells versus neurons and cell density. Granule cell migration as a measure of developmental neuronal function was analyzed in the presence of various combinations of growth factors and taurine under various depolarizing conditions (glutamate, K+). We found that K+ concentrations > 7 mM in BME and 10% horse serum blocked migration in less than 30 min. Taurine did not prevent this effect. However, in the presence of HEPES as well as in F12-medium with HEPES, taurine restored granule cell migration. On the other hand, glutamate- or NMDA-mediated depolarization stopped migrating granule cells while NMDA antagonists extended the period of migration. Taurine amplified the stop-signal in the presence of glutamate agonists but increased the number of migrating cells in the absence of glutamate. Thus, the mechanisms of glutamate receptor-mediated depolarization and K+-depolarization appear to be different. Since taurine prevents glutamate-mediated excitotoxicity, possibly by reducing Ca2+ influx under depolarizing conditions, but amplifies the stop-signal, Ca2+ levels may not control granule cell migration.


Granule Cell Horse Serum Neuronal Survival Excitatory Amino Acid Cerebellar Granule Cell 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Balazs, R., Gallo, V. and Kingsbury, A. 1988, Effect of depolarization on the maturation of cerebellar granule cells in culture. Dev. Brain Res. 40:269–279.CrossRefGoogle Scholar
  2. 2.
    Beal, M.F. 1994, Energy, oxidative damage, and Alzheimer’s disease: Clues to the underlying puzzle. Neurobiol.Aging 15:171–174.CrossRefGoogle Scholar
  3. 3.
    Bottenstein, J.E, Skaper, S.D., Varon, S.S. and Sato, G.H. 1980, Selective survival of neurons from chick embryo sensory ganglionic dissociates utilizing serum-free supplemented medium. Exp. Cell. Res. 125:183–290.CrossRefGoogle Scholar
  4. 4.
    Cameron, R.S. and Rakic, P. 1994, Identification of membrane proteins that comprise plasmalemmal junction between migrating neurons and radial glial cells. J. Neurosci. 14:3139–3155.Google Scholar
  5. 5.
    Choi, D.W. 1988, Glutamate neurotoxicity and disease of the nervous system. Neuron 1:623.CrossRefGoogle Scholar
  6. 6.
    Eimerl, S. and Schramm M. 1993, Resuscitation of brain neurons in the presence of Ca2+ after toxic NMDA receptor activity. J.Neurochem. 61:518–525.CrossRefGoogle Scholar
  7. 7.
    Feng, L. Hatten, M.E. and Heintz, N. 1994, Brain lipid-binding protein (BLBP): Anovel signalling system in the developing mammalian CNS. Neuron 12:895–908.CrossRefGoogle Scholar
  8. 8.
    Fishman, R.B. and Hatten, M.E. 1993, Multiple receptor systems promote CNS neural migration. J. Neurosci. 13:3485–3495.Google Scholar
  9. 9.
    Gallo, V., Kingsbury, A., Balazs, R. and Jorgensen, O.S. 1987, The role of depolarization in the survival and differentiation of cerebellar granule cells in culture. J.Neurosci. 7:2203–2213.Google Scholar
  10. 10.
    Ghosh, A. and Grennberg, M.E. 1995, Calcium signalling in neurons: molecular mechanisms and cellular consequences. Science 268:239–247.CrossRefGoogle Scholar
  11. 11.
    Huxtable, R.J. 1992, The physiological actions of taurine. Physiol. Rev. 72:101–163.Google Scholar
  12. 12.
    Komuro, H. and Rakic, P. 1995, Dynamics of granule cell migration: A confocal microscopic study in acute cerebellar slice preparations. J. Neurosci. 15:1110–1120.Google Scholar
  13. 13.
    Liesi, P., Seppala, I. and Trenkner, E. 1992, Neuronal migration in cerebellar microcultures is inhibited by antibodies against a neurite outgrowth domain of laminin. J. Neurosci. Res. 33:170–176.CrossRefGoogle Scholar
  14. 14.
    Lindholm, D., Dechant, G., Heisenberg, C.-P. and Thoemen, H. 1993, Brain-derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects them against glutamate-induced neurotoxicity. Eur.J.Neurosci. 5:1455–1464.CrossRefGoogle Scholar
  15. 15.
    Mattson, M.P., Lovell, M.A., Furakawa, K. and Markesberry, W. 1995, Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increased antioxidant enzyme activities in hippocampal neurons. J.Neurochem. 65:1740–1751.CrossRefGoogle Scholar
  16. 16.
    Mattson, M.P., Zhang, Y. and Bose, S. 1993, Growth factors prevent mitochondrial dysfunction, loss of calcium homeostasis, and cell injury, but not ATP depletion in hippocampal neurons deprived of glucose. Exp.Neurol. 121:1–18.CrossRefGoogle Scholar
  17. 17.
    Mattson, M.P., Guthrie, P.B., Murrain, M. and Kates, S.B. 1989, Fibroblast growth factor and glutamate: Opposing actions in the generation and degeneration of hippocampal neuroarchitecture. FABEB J. 3:2519–2526.Google Scholar
  18. 18.
    Miale, I. and Sidman, R.L. 1961, An autoradiographic analysis of histogenesis in mouse cerebellum. Exp. Neurol. 4:277–296.CrossRefGoogle Scholar
  19. 19.
    Ramon y Cajal, S. 1960, Studies on Vertebrate Neurogenesis Transi. L. Guth, Springfield, IL, p. 423.Google Scholar
  20. 20.
    Schousboe, A., Meier, E., Dreier, J. and Hertz, L. 1989, Preparation of primary cultures of mouse (rat) cerebellar granule cells, in: “A Dissection and Tissue Culture Manual of the Nervous System”, Shahar, A., DeVellis, J., Vernadakis, A. and Haber, B. eds. Alan R. Liss, New York, pp. 203–206.Google Scholar
  21. 21.
    Sidman, R.L. and Rakic, P. 1973, Neuronal migration, with special reference to developing human brain. Brain Res. 62:1–35.CrossRefGoogle Scholar
  22. 22.
    Sturman, J.A. 1993, Taurine in development. Physiol. Rev. 73:119–147.Google Scholar
  23. 23.
    Trenkner, E. and Sidman, R.L. 1977, Histogenesis of mouse cerebellum in microwell cultures: Cell reaggregation and migration, fiber and synapse formation. J. Cell Biol. 75:915–940.CrossRefGoogle Scholar
  24. 24.
    Trenkner, E., Smith D. and Segil, N. 1984, Is cerebellar granule cell migration regulated by an internal clock? J. Neurosci. 4:2850–2855.Google Scholar
  25. 25.
    Trenkner, E. 1990, The role of taurine and glutamate during early postnatal cerebellar development of neonatal and weaver mutant mice, in: “Excitatory Amino Acids and Neuronal Plasticity”, Ben-Ari, Y. ed. Plenum Press, New York, pp. 239–244.Google Scholar
  26. 26.
    Trenkner, E. 1991, Cerebellar cells in culture, in: “Culturing Nerve Cells”, Banker, G. and Goslin, K. eds. MIT Press, pp. 283-307.Google Scholar
  27. 27.
    Trenkner, E., Liu, DJ, Harris, C. and Sturman, J.A. 1994, Regulation of protein kinase C activity by taurine and β-alanine during excitotoxicity in cat and mouse cerebellar cultures, in: “Taurine in Health and Disease”, Huxtable, R.J. and Michalk, D.V. eds. Plenum Press, New York, pp. 309–316.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • E. Trenkner
    • 1
  • A. El Idrissi
    • 1
  • C. Harris
    • 1
  1. 1.New York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA

Personalised recommendations