Oligomeric Aβ25-35 induces the tyrosine phosphorylation of PSD-95 by SrcPTKs in rat hippocampal CA1 subfield.

Although amyloid-β (Aβ) is one of the neuropathological hallmarks of Alzheimer's Disease (AD), the mechanisms of Aβ neurotoxicity remain to be clarified. This study was aimed to evaluate the effect of Aβ on postsynaptic density-95 (PSD-95) tyrosine phosphorylation. Elucidating the regulatory mechanisms underlying it may be a promising therapy in AD. Aβ25-35 oligomers (20 μg/rat) were administered intracerebroventricularly in adult male Sprague-Dawley rats. PSD-95 tyrosine phosphorylation was assessed using immunoprecipitation followed by immunoblot analysis. Immunoblot was applied for measuring the protein levels of PSD-95 and β-actin. Following 3, 7, 14, 21 days after oligomeric Aβ25-35 treatment, the tyrosine phosphorylation of PSD-95 increased significantly, and peaked at 3 days after oligomeric Aβ25-35 treatment in hippocampal CA1 subfield. Src family protein tyrosine kinases (SrcPTKs) specific inhibitor PP2 attenuated the tyrosine phosphorylation of PSD-95 induced by Aβ25-35. Amantadine [N-methyl-D-aspartate (NMDA) receptor noncompetitive antagonist], NVP-AAM077 (GluN2A-containing NMDA receptor selective inhibitor) and Ro25-6981 (GluN2B-containing NMDA receptor selective inhibitor) also suppressed the Aβ25-35-induced PSD-95 tyrosine phosphorylation. These results suggest that Aβ oligomers induce the tyrosine phosphorylation of PSD-95 by SrcPTKs, which is mediated by the activation of GluN2A- and GluN2B-containing NMDA receptors.

Citation

Gui-Mei Wu, Cai-Ping Du, Yan Xu. Oligomeric Aβ25-35 induces the tyrosine phosphorylation of PSD-95 by SrcPTKs in rat hippocampal CA1 subfield. The International journal of neuroscience. 2023 Dec;133(8):888-895

Mesh Tags

Substances

PMID: 34818135

search → result