Alpha v integrins mediate beta-amyloid induced inhibition of long-term potentiation.
Beta-amyloid (Abeta) is the principal component of the extracellular plaques present in patients with Alzheimer's disease. Several studies have recently shown that acutely applied Abeta inhibits the induction of LTP in the hippocampus. In the present studies, we have investigated the role of integrins in such Abeta-mediated block of LTP in the dentate gyrus in vitro and in the CA1 in vivo. Selective antibodies to the alpha v integrin subunit were found to prevent the Abeta 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 Abeta. In addition, a small molecule nonpeptide antagonist of alpha v-containing integrins and two other antagonistic ligands of integrins, superfibronectin and the disintegrin echistatin, also prevented the Abeta inhibition of LTP. These studies indicate that alpha v integrins may be important mediators of synaptic dysfunction prior to neurodegeneration in Alzheimer's disease.
Wang
Qinwen
Q
Department of Physiology, Trinity College, Dublin 2, Ireland.
Klyubin
Igor
I
Wright
Sarah
S
Griswold-Prenner
Irene
I
Rowan
Michael J
MJ
Anwyl
Roger
R
D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018891:Dentate Gyrus / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D039564:Integrin alphaV / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D016229:Amyloid beta-Peptides; D000906:Antibodies; D039564:Integrin alphaV; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D010455:Peptides; C057986:echistatin