Hypoxia-ischemia modifies postsynaptic GluN2B-containing NMDA receptor complexes in the neonatal mouse brain

Fuxin Lu, Guo Shao, Yongqiang Wang, Shenheng Guan, Alma L. Burlingame, Xuemei Liu, Xiao Liang, Renatta Knox, Donna M. Ferriero, Xiangning Jiang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The N-methyl-D-aspartate-type glutamate receptor (NMDAR)-associated multiprotein complexes are indispensable for synaptic plasticity and cognitive functions. While purification and proteomic analyses of these signaling complexes have been performed in adult rodent and human brain, much less is known about the protein composition of NMDAR complexes in the developing brain and their modifications by neonatal hypoxic-ischemic (HI) brain injury. In this study, the postsynaptic density proteins were prepared from postnatal day 9 naïve, sham-operated and HI-injured mouse cortex. The GluN2B-containing NMDAR complexes were purified by immunoprecipitation with a mouse GluN2B antibody and subjected to mass spectrometry analysis for determination of the GluN2B binding partners. A total of 71 proteins of different functional categories were identified from the naïve animals as native GluN2B-interacting partners in the developing mouse brain. Neonatal HI reshaped the postsynaptic GluN2B interactome by recruiting new proteins, including multiple kinases, into the complexes; and modifying the existing associations within 1 h of reperfusion. The early responses of postsynaptic NMDAR complexes and their related signaling networks may contribute to molecular processes leading to cell survival or death, brain damage and/or neurological disorders in term infants with neonatal encephalopathy.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalExperimental Neurology
Volume299
DOIs
StatePublished - Jan 2018

Keywords

  • Brain
  • Development
  • Hypoxia/ischemia
  • NMDA receptors
  • Proteomics

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