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

A putative tetrapeptide beta-amyloid (A beta) antagonist (propionyl-Ile-Ile-Gly-Leu [Pr-IIGL]) based on the [31-34] sequence of A beta was previously shown to rescue astrocytes from A beta-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 A beta(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 A beta(1-42)induced increases in extracellular aspartate and glutamate concentrations in the MEN, 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 A beta antagonists in ameliorating A beta excitotoxicity in vivo. NeuroReport 10:1693-1698 (C) 1999 Lippincott Williams & Wilkins.