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

• Published in: Journal of neuroscience research Vol. 93; no. 12; pp. 1865 - 1873
• Main Authors: Safina, Dina R., Surin, Alexander M., Pinelis, Vsevolod G., Kostrov, Sergey V.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2015; Wiley Subscription Services, Inc
• Subjects: Animals; Animals, Newborn; Calcium - metabolism; calcium homeostasis; Cells, Cultured; Cerebellum - cytology; glutamate excitotoxicity; Glutamic Acid - pharmacology; Homeostasis - drug effects; Humans; Male; neurons; Neurons - drug effects; Neurotrophin 3 - metabolism; neurotrophins; proneurotrophins; Protein Precursors - metabolism; Rats; glutamate excitotoxicity; calcium homeostasis; neurons; neurotrophins; proneurotrophins
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23667

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 µM) 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 Са2+ homeostasis in the presence of pro‐NT‐3 likely are due to the decreased rate of Са2+ removal from the cytosol during the DCD latency period. © 2015 Wiley Periodicals, Inc. This article presents a study of the impact of neurotrophin‐3 (NT‐3) and its precursor pro‐NT‐3 on abnormal calcium homeostasis in rat cerebellar cells with excessively stimulated Glu receptors. Analysis of the processes mediated by neurotrophic factors can extend our knowledge of the activity of these proteins and the nervous system in general.