Fibrillar Aβ1-42 enhances NMDA receptor sensitivity via the integrin signaling pathway

Gábor J. Uhász, Balázs Barkóczi, Gabriella Vass, Zsolt Datki, Ákos Hunya, L. Fülöp, D. Budai, B. Penke, Viktor Szegedi

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 Aβ 1-42 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 Aβ 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 Aβ1-42 is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.

Original languageEnglish
Pages (from-to)1055-1067
Number of pages13
JournalJournal of Alzheimer's Disease
Volume19
Issue number3
DOIs
Publication statusPublished - 2010

Fingerprint

N-Methylaspartate
Integrins
src-Family Kinases
Blocking Antibodies
Electrophysiology
Neutralizing Antibodies
Amyloid
Phosphorylation
aspartic acid receptor
Calcium
Neurons

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Calcium influx
  • Integrin
  • NMDA receptor
  • Single-unit
  • Src kinase

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology
  • Medicine(all)

Cite this

Fibrillar Aβ1-42 enhances NMDA receptor sensitivity via the integrin signaling pathway. / Uhász, Gábor J.; Barkóczi, Balázs; Vass, Gabriella; Datki, Zsolt; Hunya, Ákos; Fülöp, L.; Budai, D.; Penke, B.; Szegedi, Viktor.

In: Journal of Alzheimer's Disease, Vol. 19, No. 3, 2010, p. 1055-1067.

Research output: Contribution to journalArticle

Uhász, Gábor J. ; Barkóczi, Balázs ; Vass, Gabriella ; Datki, Zsolt ; Hunya, Ákos ; Fülöp, L. ; Budai, D. ; Penke, B. ; Szegedi, Viktor. / Fibrillar Aβ1-42 enhances NMDA receptor sensitivity via the integrin signaling pathway. In: Journal of Alzheimer's Disease. 2010 ; Vol. 19, No. 3. pp. 1055-1067.
@article{bab906b21e2143a793a54302acc0d4c2,
title = "Fibrillar Aβ1-42 enhances NMDA receptor sensitivity via the integrin signaling pathway",
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 Aβ 1-42 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 Aβ 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 Aβ1-42 is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.",
keywords = "Alzheimer's disease, Amyloid-β, Calcium influx, Integrin, NMDA receptor, Single-unit, Src kinase",
author = "Uh{\'a}sz, {G{\'a}bor J.} and Bal{\'a}zs Bark{\'o}czi and Gabriella Vass and Zsolt Datki and {\'A}kos Hunya and L. F{\"u}l{\"o}p and D. Budai and B. Penke and Viktor Szegedi",
year = "2010",
doi = "10.3233/JAD-2010-1301",
language = "English",
volume = "19",
pages = "1055--1067",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "3",

}

TY - JOUR

T1 - Fibrillar Aβ1-42 enhances NMDA receptor sensitivity via the integrin signaling pathway

AU - Uhász, Gábor J.

AU - Barkóczi, Balázs

AU - Vass, Gabriella

AU - Datki, Zsolt

AU - Hunya, Ákos

AU - Fülöp, L.

AU - Budai, D.

AU - Penke, B.

AU - Szegedi, Viktor

PY - 2010

Y1 - 2010

N2 - 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 Aβ 1-42 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 Aβ 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 Aβ1-42 is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.

AB - 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 Aβ 1-42 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 Aβ 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 Aβ1-42 is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation.

KW - Alzheimer's disease

KW - Amyloid-β

KW - Calcium influx

KW - Integrin

KW - NMDA receptor

KW - Single-unit

KW - Src kinase

UR - http://www.scopus.com/inward/record.url?scp=77149131235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77149131235&partnerID=8YFLogxK

U2 - 10.3233/JAD-2010-1301

DO - 10.3233/JAD-2010-1301

M3 - Article

C2 - 20157259

AN - SCOPUS:77149131235

VL - 19

SP - 1055

EP - 1067

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 3

ER -