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In the central nervous system, the formation and maintenance of neuronal connections are regulated, in part, through a balanced interaction between intracellular and extracellular signals. Under physiological conditions, these signals regulate neuronal maturation, survival and function. Slight changes of this balance however, result in significant functional and structural changes, leading to pathological conditions, loss of function and subsequently to cell death. Prominent among these signals are growth factors and neuroactive amino acids (NAAs). The purpose of these studies was to examine the combined effects of growth factors (Gfs) and neuroactive amino acids (NAAs) on mouse cerebellar granule cells (CGC) survival, energy-metabolism, calcium homeostasis, and protein phosphorylation. We have demonstrated that taurine at physiological concentrations had a neurotrophic effect and protected neurons against glutamate excitotoxicity. These effects were partially mediated through the modulation of intracellular calcium homeostasis34,17. Here we report that also cellular energy metabolism was affected by taurine. Furthermore, as a consequence of its calcium modulatory role, taurine regulated protein kinase C (PKC) activity during glutamate depolarization. Finally, taurine down-regulated the glutamate-induced phosphorylation of a specific set of proteins. We further demonstrated that these various effects of taurine were selectively modulated by brain-derived neurotropic factor (BDNF) and basic fibroblast growth factor (bFGF), suggesting that NAAs, the mitochondrial energy-metabolism and growth factors together regulate neuronal survival and function. It is, therefore, of considerable importance to identify the different environmental signals that interact to regulate the development and maintenance of the integrity of neuronal functions, in order to better understand mechanisms that could lead to abnormal development. |
