Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis

Tibor Harkany, István Ábrahám, Gábor Laskay, Wia Timmerman, Krisztina Jost, Márta Zarándi, B. Penke, C. Nyakas, Paul G M Luiten

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A putative tetrapeptide β-amyloid (Aβ) antagonist (propionyl-Ile-Ile- Gly-Leu [Pr-IIGL]) based on the [3134] sequence of Aβ was previously shown to rescue astrocytes from Aβ-induced membrane depolarization and subsequent long-term elevations of the intracellular Ca2+ concentration in vitro. Here we provide in vivo evidence that the Pr-IIGL tetrapeptide effectively attenuates the excitotoxic action of Aβ(1-42) on cholinergic neurons of the rat magnocellular nucleus basalis (MBN). We also demonstrate by means of microdialysis that administration of Pr-IIGL abolished Aβ(1-42)induced increases in extracellular aspartate and glutamate concentrations in the MBN, which coincide with a significant preservation of cholinergic MBN neurons and their cortical projections. This neuroprotective effect was associated with preserved exploratory behavior in an open-field paradigm, and improved memory retention in a step-through passive avoidance task. Our data presented here indicate for the first time the efficacy of short, modified functional Aβ antagonists in ameliorating Aβ excitotoxicity in vivo.

Original languageEnglish
Pages (from-to)1693-1698
Number of pages6
JournalNeuroReport
Volume10
Issue number8
Publication statusPublished - Jun 3 1999

Fingerprint

Cholinergic Neurons
Amyloid
Exploratory Behavior
Microdialysis
Neuroprotective Agents
Aspartic Acid
Astrocytes
Glutamic Acid
Membranes
In Vitro Techniques
Retention (Psychology)

Keywords

  • β-Amyloid
  • Excitotoxicity
  • Glutamate
  • Learning and memory
  • NMDA receptor
  • Tetrapeptide antagonist

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Harkany, T., Ábrahám, I., Laskay, G., Timmerman, W., Jost, K., Zarándi, M., ... Luiten, P. G. M. (1999). Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis. NeuroReport, 10(8), 1693-1698.

Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis. / Harkany, Tibor; Ábrahám, István; Laskay, Gábor; Timmerman, Wia; Jost, Krisztina; Zarándi, Márta; Penke, B.; Nyakas, C.; Luiten, Paul G M.

In: NeuroReport, Vol. 10, No. 8, 03.06.1999, p. 1693-1698.

Research output: Contribution to journalArticle

Harkany, T, Ábrahám, I, Laskay, G, Timmerman, W, Jost, K, Zarándi, M, Penke, B, Nyakas, C & Luiten, PGM 1999, 'Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis', NeuroReport, vol. 10, no. 8, pp. 1693-1698.
Harkany T, Ábrahám I, Laskay G, Timmerman W, Jost K, Zarándi M et al. Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis. NeuroReport. 1999 Jun 3;10(8):1693-1698.
Harkany, Tibor ; Ábrahám, István ; Laskay, Gábor ; Timmerman, Wia ; Jost, Krisztina ; Zarándi, Márta ; Penke, B. ; Nyakas, C. ; Luiten, Paul G M. / Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis. In: NeuroReport. 1999 ; Vol. 10, No. 8. pp. 1693-1698.
@article{6b4f07a380da450fa81673ab9c75cc7f,
title = "Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis",
abstract = "A putative tetrapeptide β-amyloid (Aβ) antagonist (propionyl-Ile-Ile- Gly-Leu [Pr-IIGL]) based on the [3134] sequence of Aβ was previously shown to rescue astrocytes from Aβ-induced membrane depolarization and subsequent long-term elevations of the intracellular Ca2+ concentration in vitro. Here we provide in vivo evidence that the Pr-IIGL tetrapeptide effectively attenuates the excitotoxic action of Aβ(1-42) on cholinergic neurons of the rat magnocellular nucleus basalis (MBN). We also demonstrate by means of microdialysis that administration of Pr-IIGL abolished Aβ(1-42)induced increases in extracellular aspartate and glutamate concentrations in the MBN, which coincide with a significant preservation of cholinergic MBN neurons and their cortical projections. This neuroprotective effect was associated with preserved exploratory behavior in an open-field paradigm, and improved memory retention in a step-through passive avoidance task. Our data presented here indicate for the first time the efficacy of short, modified functional Aβ antagonists in ameliorating Aβ excitotoxicity in vivo.",
keywords = "β-Amyloid, Excitotoxicity, Glutamate, Learning and memory, NMDA receptor, Tetrapeptide antagonist",
author = "Tibor Harkany and Istv{\'a}n {\'A}brah{\'a}m and G{\'a}bor Laskay and Wia Timmerman and Krisztina Jost and M{\'a}rta Zar{\'a}ndi and B. Penke and C. Nyakas and Luiten, {Paul G M}",
year = "1999",
month = "6",
day = "3",
language = "English",
volume = "10",
pages = "1693--1698",
journal = "NeuroReport",
issn = "0959-4965",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Propionyl-IIGL tetrapeptide antagonizes β-amyloid excitotoxicity in rat nucleus basalis

AU - Harkany, Tibor

AU - Ábrahám, István

AU - Laskay, Gábor

AU - Timmerman, Wia

AU - Jost, Krisztina

AU - Zarándi, Márta

AU - Penke, B.

AU - Nyakas, C.

AU - Luiten, Paul G M

PY - 1999/6/3

Y1 - 1999/6/3

N2 - A putative tetrapeptide β-amyloid (Aβ) antagonist (propionyl-Ile-Ile- Gly-Leu [Pr-IIGL]) based on the [3134] sequence of Aβ was previously shown to rescue astrocytes from Aβ-induced membrane depolarization and subsequent long-term elevations of the intracellular Ca2+ concentration in vitro. Here we provide in vivo evidence that the Pr-IIGL tetrapeptide effectively attenuates the excitotoxic action of Aβ(1-42) on cholinergic neurons of the rat magnocellular nucleus basalis (MBN). We also demonstrate by means of microdialysis that administration of Pr-IIGL abolished Aβ(1-42)induced increases in extracellular aspartate and glutamate concentrations in the MBN, which coincide with a significant preservation of cholinergic MBN neurons and their cortical projections. This neuroprotective effect was associated with preserved exploratory behavior in an open-field paradigm, and improved memory retention in a step-through passive avoidance task. Our data presented here indicate for the first time the efficacy of short, modified functional Aβ antagonists in ameliorating Aβ excitotoxicity in vivo.

AB - A putative tetrapeptide β-amyloid (Aβ) antagonist (propionyl-Ile-Ile- Gly-Leu [Pr-IIGL]) based on the [3134] sequence of Aβ was previously shown to rescue astrocytes from Aβ-induced membrane depolarization and subsequent long-term elevations of the intracellular Ca2+ concentration in vitro. Here we provide in vivo evidence that the Pr-IIGL tetrapeptide effectively attenuates the excitotoxic action of Aβ(1-42) on cholinergic neurons of the rat magnocellular nucleus basalis (MBN). We also demonstrate by means of microdialysis that administration of Pr-IIGL abolished Aβ(1-42)induced increases in extracellular aspartate and glutamate concentrations in the MBN, which coincide with a significant preservation of cholinergic MBN neurons and their cortical projections. This neuroprotective effect was associated with preserved exploratory behavior in an open-field paradigm, and improved memory retention in a step-through passive avoidance task. Our data presented here indicate for the first time the efficacy of short, modified functional Aβ antagonists in ameliorating Aβ excitotoxicity in vivo.

KW - β-Amyloid

KW - Excitotoxicity

KW - Glutamate

KW - Learning and memory

KW - NMDA receptor

KW - Tetrapeptide antagonist

UR - http://www.scopus.com/inward/record.url?scp=0033519547&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033519547&partnerID=8YFLogxK

M3 - Article

C2 - 10501559

AN - SCOPUS:0033519547

VL - 10

SP - 1693

EP - 1698

JO - NeuroReport

JF - NeuroReport

SN - 0959-4965

IS - 8

ER -