BDNF Contributes to Spinal Long-Term Potentiation and Mechanical Hypersensitivity Via Fyn-Mediated Phosphorylation of NMDA Receptor GluN2B Subunit at Tyrosine 1472 in Rats Following Spinal Nerve Ligation

Neurochemical Research
Song LiGuogang Xing

Abstract

Previously we have demonstrated that brain-derived neurotrophic factor (BDNF) contributes to spinal long-term potentiation (LTP) and pain hypersensitivity through activation of GluN2B-containing N-methyl-D-aspartate (GluN2B-NMDA) receptors in rats following spinal nerve ligation (SNL). However, the molecular mechanisms by which BDNF impacts upon GluN2B-NMDA receptors and spinal LTP still remain unclear. In this study, we first documented that Fyn kinase-mediated phosphorylation of GluN2B subunit at tyrosine 1472 (pGluN2BY1472) was involved in BDNF-induced spinal LTP and pain hypersensitivity in intact rats. Second, we revealed a co-localization of Fyn and GluN2B-NMDA receptor in cultured dorsal horn neurons, implying that Fyn is a possible intermediate kinase linking BDNF/TrkB signaling with GluN2B-NMDA receptors in the spinal dorsal horn. Furthermore, we discovered that both SNL surgery and intrathecal active Fyn could induce an increased expression of dorsal horn pGluN2BY1472, as well as pain hypersensitivity in response to von Frey filaments stimuli; and more importantly, all these actions were effectively abrogated by pre-treatment with either PP2 or ifenprodil to respectively inhibit Fyn kinase and GluN2B-NMDA receptors ac...Continue Reading

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Citations

Jul 11, 2018·Cellular Reprogramming·Yingjia YaoJingxian Yang
Apr 16, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Hsiang-Chun LaiChing-Liang Hsieh
Oct 26, 2020·Molecular Neurobiology·Yanling LiangYinghong Tian
May 23, 2021·Neuroscience Letters·Wu ZhouJianguo Yao
Jun 24, 2021·Chemical Senses·Dane Kim, Richard L Doty

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

GraphPad Prism
GraphPad
Spike2

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