Document Detail

Propionyl-IIGL tetrapeptide antagonizes beta-amyloid excitotoxicity in rat nucleus basalis.
MedLine Citation:
PMID:  10501559     Owner:  NLM     Status:  MEDLINE    
A putative tetrapeptide beta-amyloid (Abeta) antagonist (propionyl-Ile-Ile-Gly-Leu [Pr-IIGL]) based on the [31-34] sequence of Abeta was previously shown to rescue astrocytes from Abeta-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 Abeta(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 Abeta(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 Abeta antagonists in ameliorating Abeta excitotoxicity in vivo.
T Harkany; I Abrahám; G Laskay; W Timmerman; K Jost; M Zarándi; B Penke; C Nyakas; P G Luiten
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neuroreport     Volume:  10     ISSN:  0959-4965     ISO Abbreviation:  Neuroreport     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-11-15     Completed Date:  1999-11-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9100935     Medline TA:  Neuroreport     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1693-8     Citation Subset:  IM    
Department of Animal Physiology, University of Groningen, Haren, The Netherlands.
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MeSH Terms
Acetylcholinesterase / metabolism
Amyloid beta-Protein / antagonists & inhibitors,  toxicity*
Aspartic Acid / metabolism
Avoidance Learning / drug effects
Basal Nucleus of Meynert / anatomy & histology,  drug effects*,  metabolism
Behavior, Animal / drug effects
Extracellular Space / drug effects,  metabolism
Glutamic Acid / metabolism
Motor Activity / drug effects
Neuroprotective Agents / pharmacology*
Oligopeptides / pharmacology*
Peptide Fragments / antagonists & inhibitors,  toxicity*
Rats, Wistar
Taurine / metabolism
Reg. No./Substance:
0/Amyloid beta-Protein; 0/Neuroprotective Agents; 0/Oligopeptides; 0/Peptide Fragments; 0/amyloid beta-protein (1-42); 0/propionyl-isoleucyl-isoleucyl-glycyl-leucinamide; 107-35-7/Taurine; 56-84-8/Aspartic Acid; 56-86-0/Glutamic Acid; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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