Fibrillar A beta(1-42) enhances NMDA receptor sensitivity via the integrin signaling pathway

The aggregated form of amyloid-beta (Abeta) (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 electrophysi...

Full description

Saved in:
Bibliographic Details
Main Authors: Juhász Gábor
Barkóczi Balázs
Vass Gabriella
Datki Zsolt László
Hunya Ákos
Fülöp Lívia
Budai Dénes
Penke Botond
Szegedi Viktor
Format: Article
Published: 2010
Series:Journal of Alzheimer's disease : JAD 19 No. 3
doi:10.3233/JAD-2009-1301

mtmt:1361260
Online Access:http://publicatio.bibl.u-szeged.hu/9338
Description
Summary:The aggregated form of amyloid-beta (Abeta) (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 Ca (2+) measurements. Pretreatment of differentiated SH-SY5Y cells with fibrillar Abeta (1-42) markedly enhanced the intracellular calcium increases caused by NMDA receptor (NMDA-R) stimulation. Function blocking antibody against beta1 integrin depressed the facilitatory effects of Abeta (1-42). Similarly, Abeta (1-42) facilitated NMDA-R driven firing of hippocampal neurons in vivo, and this effect was reduced by neutralizing antibody against beta1 integrins. The positive action of Abeta (1-42) on NMDA-R dependent responses was also depressed by an inhibitor known to block Src kinase. These results support the hypothesis that aggregated Abeta (1-42) is recognized by the beta1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.
Physical Description:1055-1067
ISSN:1875-8908