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The Journal of Neuroscience, November 1, 1999, 19(21):9459-9468

Growth Factors and Taurine Protect against Excitotoxicity by Stabilizing Calcium Homeostasis and Energy Metabolism

Abdeslem El Idrissi and Ekkhart Trenkner

New York State Institute for Basic Research in Developmental Disabilities, Center for Developmental Neuroscience, The Graduate School and University Center of the City University of New York, Staten Island, New York 10314

Taurine, brain derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF) are known to control the development of early postnatal cerebellar granule cells. This study attempted to investigate possible mechanisms of this control by determining neuronal survival, calcium homeostasis, and related calcium-mediated functions, as well as the site of action during glutamate-induced excitotoxicity in cultures of cerebellar granule cells. We report that stimulation of glutamate receptors induced a rapid increase in intracellular calcium concentrations ([Ca2+]i) and a decrease in mitochondrial energy metabolism. These effects of glutamate were time- and concentration-dependent and could be specifically blocked by glutamate receptor antagonists. Taurine and bFGF but not BDNF differently regulated [Ca2+]i, and preserved the mitochondrial energy metabolism in the presence of glutamate. The regulation of [Ca2+]i by bFGF and taurine required pretreatment of cells with these factors. Confocal microscope analysis of [Ca2+]i and 45Ca2+ uptake studies showed that bFGF reduced the magnitude of glutamate-induced calcium uptake with no apparent regulation thereafter. Taurine, on the other hand, did not affect the level of calcium uptake induced by glutamate but rather the duration of the maximal response; this maximal response was transient and returned to basal levels ~10 min after glutamate receptor stimulation. We conclude from these data that bFGF and taurine prevent glutamate excitotoxicity through regulation of [Ca2+]i and mitochondrial energy metabolism. Furthermore, the neuroprotective role of taurine and bFGF was enhanced by their collaboration.

Key words: cerebellar granule cells; excitotoxicity; growth factors; taurine; glutamate; calcium; energy metabolism; BDNF; bFGF


Copyright © 1999 Society for Neuroscience  0270-6474/99/19219459-10$05.00/0


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