Activation of CaMKII and GluR1 by the PSD-95-GluN2B coupling-dependent phosphorylation of glun2b in the spinal cord in a rat model of type-2 diabetic neuropathic pain

Ya Bing Zhu, Gai Li Jia, Jun Wu Wang, Xiu Ying Ye, Jia Hui Lu, Jia Li Chen, Mao Biao Zhang, Ci Shan Xie, Yu Jing Shen, Yuan Xiang Tao, Jun Li, Hong Cao

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The mechanisms underlying type-2 diabetic neuropathic pain (DNP) are unclear. This study investigates the coupling of postsynaptic density-95 (PSD-95) to N-methyl-D-aspartate receptor subunit 2B (GluN2B), and the subsequent phosphorylation of GluN2B (Tyr1472-GluN2B) in the spinal cord in a rat model of type-2 DNP. Expression levels of PSD-95, Tyr1472-GluN2B, Ca/calmodulindependent protein kinase II (CaMKII) and its phosphorylated counterpart (Thr286-CaMKII), and a-amino-3-hydroxy-5-methyl-4-soxazole propionic acid receptor subtype 1 (GluR1) and its phosphorylated counterpart (Ser831-GluR1) were significantly increased versus controls in the spinal cord of type-2 DNP rats whereas the expression of total spinal GluN2B did not change. The intrathecal injection of Ro25-6981 (a specific antagonist of GluN2B) or Tat-NR2B9c (a mimetic peptide disrupting the interaction between PSD-95 and GluN2B) induced an antihyperalgesic effect and blocked the increased expression of Tyr1472-GluN2B, CaMKII, GluR1, Thr286-CaMKII, and Ser831-GluR1 in the spinal cords; the increase in spinal cord PSD-95 was not affected. These findings indicate that the PSD-95-GluN2B interaction may increase phosphorylation of GluN2B, and subsequently induce the expression of phosphorylation of CaMKII and GluR1 in the spinal cord of type-2 DNP rats. Targeting the interaction of PSD-95 with GluN2B may provide a new therapeutic strategy for type-2 DNP.

Original languageEnglish (US)
Pages (from-to)800-808
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume79
Issue number7
DOIs
StatePublished - Jul 1 2020

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Keywords

  • Diabetes
  • GluN2B
  • Neuropathic pain
  • PSD-95
  • Spinal cord

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