Effect of neurotrophin-3 precursor on glutamate-induced calcium homeostasis deregulation in rat cerebellum granule cells

Neurotrophin-3 (NT-3) belongs to the family of highly conserved dimeric growth factors that controls the differentiation and activity of various neuronal populations. Mammals contain both the mature (NT-3) and the precursor (pro-NT-3) forms of neurotrophin. Members of the neurotrophin family are involved in the regulation of calcium homeostasis in neurons; however, the role of NT-3 and pro-NT-3 in this process remains unclear. The current study explores the effects of NT-3 and pro-NT-3 on disturbed calcium homeostasis and decline of mitochondrial potential induced by a neurotoxic concentration of glutamate (Glu; 100 mu M) in the primary culture of rat cerebellar granule cells. In this Glu excitotoxicity model, mature NT-3 had no effect on the induced changes in Ca2+ homeostasis. In contrast, pro-NT-3 decreased the period of delayed calcium deregulation (DCD) and concurrent strong mitochondrial depolarization. According to the amplitude of the increase in the intracellular free Ca2+ concentration ([Ca2+](i)) and Fura-2 fluorescence quenching by Mn2+ within the first 20 sec of exposure to Glu, pro-NT-3 had no effect on the initial rate of Ca2+ entry into neurons. During the lag period preceding DCD, the mean amplitude of [Ca2+](i) rise was 1.2-fold greater in the presence of pro-NT-3 than in the presence of Glu alone (1.67 +/- 0.07 and 1.39 +/- 0.04, respectively, P<0.05). The Glu-induced changes in Ca2+ homeostasis in the presence of pro-NT-3 likely are due to the decreased rate of Ca2+ removal from the cytosol during the DCD latency period. (c) 2015 Wiley Periodicals, Inc.