Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10223137 | Neuroscience | 2018 | 12 Pages |
Abstract
Hepatic ischemia reperfusion (HIR) has been found to induce hippocampus injury and cognitive dysfunction. The N-methyl-d-aspartate (NMDA) receptor subunit 2A (NR2A) is an important factor mediating excitotoxicity and neurons injury, and autophosphorylation of Src can up-regulate tyrosine phosphorylation of NR2A to improve its activity. However, the role of Src and NR2A in HIR-induced hippocampus injury in young mice remains unknown. In this study, we found that serum biomarkers of brain injury (S100β and NSE) increased significantly and reached highest after reperfusion of 3â¯days which had the same trend with the levels of p-Src and p-NR2A. Interactions between Src and NR2A or PSD95 were increased after HIR. Hippocampal neuron apoptosis was increased, and long-term cognitive impairment was found after reperfusion of 1â¯month. Inhibition of Src and NR2A with PP2 and NVP-AAM077 respectively not only down-regulated the levels of p-Src and p-NR2A, but also ameliorated hippocampal neurons apoptosis and long-term cognitive impairment after HIR. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-6 were increased after reperfusion of 3â¯days, while PP2 and NVP-AAM077 treatment didn't attenuate the changes. And no difference was found in serum TNF-α, IFN-γ, IL-6 concentrations as well as the levels of Src, p-Src, NR2A, p-NR2A, PSD95 among the four groups after reperfusion of 1â¯month. In summary, HIR can lead to hippocampus injury and long-term cognitive dysfunction, and Src-PSD95-NR2A pathway plays an important role in the process.
Keywords
IQRapoptosis indexHepatic ischemia reperfusionHIRNR2APSD95MWMIFN-γN-methyl-d-aspartateNMDAPMSFALTSRCEGTAIL-6HEPESNSE4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidBDNFASTAspartate aminotransferaseAlanine aminotransferaseenzyme linked immunosorbent assayEDTAEthylenediaminetetraacetic acidinterferon-γinterleukin-6analysis of varianceANOVAELISAtumor necrosis factor αCognitive functionBrain-derived neurotrophic factorTNF-αTyrosine phosphorylationphenylmethyl sulfonylfluorideMorris water mazeinterquartile rangeHippocampuspostsynaptic density protein 95
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Authors
Xiangyang Yu, Lili Jia, Kuoqi Yin, Jingshu Lv, Wenli Yu, Hongyin Du,