| First Author | Yu X | Year | 2018 |
| Journal | Neuroscience | Volume | 391 |
| Pages | 1-12 | PubMed ID | 30213765 |
| Mgi Jnum | J:267040 | Mgi Id | MGI:6257233 |
| Doi | 10.1016/j.neuroscience.2018.08.034 | Citation | Yu X, et al. (2018) Src is Implicated in Hepatic Ischemia Reperfusion-Induced Hippocampus Injury and Long-Term Cognitive Impairment in Young Mice via NMDA Receptor Subunit 2A Activation. Neuroscience 391:1-12 |
| abstractText | 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 (S100beta and NSE) increased significantly and reached highest after reperfusion of 3days 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 1month. 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 alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin (IL)-6 were increased after reperfusion of 3days, while PP2 and NVP-AAM077 treatment didn't attenuate the changes. And no difference was found in serum TNF-alpha, IFN-gamma, IL-6 concentrations as well as the levels of Src, p-Src, NR2A, p-NR2A, PSD95 among the four groups after reperfusion of 1month. 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. |
