BDNF induces sustained intracellular Ca2+ elevation through the upregulation of surface TRPC3 channels in rodent microglia [Membrane Biology]

May 8th, 2014 by Mizoguchi, Y., Kato, T. A., Seki, Y., Ohgidani, M., Sagata, N., Horikawa, H., Yamauchi, Y., Sato-Kasai, M., Hayakawa, K., Inoue, R., Kanba, S., Monji, A.

Background: Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO) and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. Results: In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca2+]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca2+ elevation. Immunocytochemical technique and flowcytometry also revealed that BDNF rapidly upregulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca2+ elevation through the upregulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. Conclusions: We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.
  • Posted in Journal of Biological Chemistry, Publications
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