αv integrins mediate beta-amyloid induced inhibition of long-term potentiation

Wang, Qinwen; Klyubin, Igor; Wright, Sarah; Griswold-Prenner, Irene; Rowan, Michael J.; Anwyl, Roger

doi:10.1016/j.neurobiolaging.2007.03.018

« Previous Next »Neurobiology of Aging
Volume 29, Issue 10 , Pages 1485-1493, October 2008

αv integrins mediate beta-amyloid induced inhibition of long-term potentiation

Qinwen Wang
- Department of Physiology, Trinity College, Dublin 2, Ireland
- These authors contributed equally to the work.
- Present address: Department of Physiology and Pharmacology, The Medical School, Ningbo University, Ningbo, China.
Igor Klyubin
- Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
- These authors contributed equally to the work.
Sarah Wright
- Elan Pharmaceuticals, 1000 Gateway Boulevard, South San Francisco, CA 94080, USA
Irene Griswold-Prenner
- Elan Pharmaceuticals, 1000 Gateway Boulevard, South San Francisco, CA 94080, USA
Michael J. Rowan
- Department of Pharmacology and Therapeutics, Trinity College, Dublin 2, Ireland
- These authors contributed equally to the work.
Roger Anwyl
- Department of Physiology, Trinity College, Dublin 2, Ireland
- These authors contributed equally to the work.
- Corresponding author. Tel.: +353 18961624.

Received 12 January 2007; received in revised form 13 March 2007; accepted 17 March 2007. published online 24 April 2007.

Abstract

Beta-amyloid (Aβ) is the principal component of the extracellular plaques present in patients with Alzheimer's disease. Several studies have recently shown that acutely applied Aβ inhibits the induction of LTP in the hippocampus. In the present studies, we have investigated the role of integrins in such Aβ-mediated block of LTP in the dentate gyrus in vitro and in the CA1 in vivo. Selective antibodies to the αv integrin subunit were found to prevent the Aβ inhibition of LTP, both in the dentate gyrus in vitro and in the CA1 in vivo. In contrast, two control antibodies did not prevent such action of Aβ. In addition, a small molecule nonpeptide antagonist of αv-containing integrins and two other antagonistic ligands of integrins, superfibronectin and the disintegrin echistatin, also prevented the Aβ inhibition of LTP. These studies indicate that αv integrins may be important mediators of synaptic dysfunction prior to neurodegeneration in Alzheimer's disease.

Keywords: Beta-amyloid, Alzheimer's disease, αv integrin, LTP, Hippocampus