Affiliations: [a] Department of Medical Chemistry, University of Szeged, Szeged, H-6720, Hungary | [b] Bay Zoltán Foundation of Applied Research – BAYGEN Institute, Szeged, H-6727, Hungary | [c] Department of Environmental Biology, University of Szeged, Szeged, H-6726, Hungary
Correspondence:
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Correspondence to: Viktor Szegedi Ph.D., Bay Zoltán Foundation of Applied Research – BAYGEN Institute, Szeged, Derkovits avenue 2., H-6727, Hungary. Tel.: +36 62 546788; Fax: +36 62 546974; E-mail: [email protected].
Note: [] Handling Associate Editor: Ashley Bush
Abstract: The aggregated form of amyloid-β (Aβ)1-42 has been shown to increase N-methyl-D-aspartic acid (NMDA) evoked neuronal activity in vivo. Here we further characterized this phenomenon by investigating the role of integrin activation and downstream Src kinase activity using in vivo electrophysiology and in vitro intracellular Ca2+ measurements. Pretreatment of differentiated SH-SY5Y cells with fibrillar Aβ1-42 markedly enhanced the intracellular calcium increases caused by NMDA receptor (NMDA-R) stimulation. Function blocking antibody against β1 integrin depressed the facilitatory effects of Aβ1-42. Similarly, Aβ1-42 facilitated NMDA-R driven firing of hippocampal neurons in vivo, and this effect was reduced by neutralizing antibody against β1 integrins. The positive action of Aβ1-42 on NMDA-R dependent responses was also depressed by an inhibitor known to block Src kinase. These results support the hypothesis that aggregated Aβ1-42 is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.
