Analysis of the effects of amyloid-beta in rat brain : effect of treatment with a novel anti-inflammatory agent VP025

Abstract

The data presented indicate that long-term potentiation was significantly impaired following acute intracerebroventricular injection of amyloid-β1-40 in rat. Similarly chronic intracerebroventricular infusion of amyloid-β1-40/amyloid-β1-42 in rat for 8, 20 or 28 days led to a deficit in long-term potentiation which was more pronounced with longer exposure to amyloid-β. Pre-treatment of rats with VP025 attenuated the amyloid-β- induced deficit in long-term potentiation. Significantly VP025 also attenuated the effects of amyloid-β on long-term potentiation, even when treatment was given following 14 days of Aβ administration. Acute and chronic infusion of amyloid-β1-40/amyloid-β1-42 also resulted in increased expression of markers of microglial activation, cluster of differentiation 86 and intracellular adhesion molecule-1, in rat hippocampus. Evidence indicates that these amyloid-(3-induced changes were also attenuated by pre-treatment wilh VP025, suggesting a coupling between microglial activation and impairment in long-term potentiation. Further analysis of the effect of amyloid-β revealed that it triggered activation of caspases-8 and -3 in cortical tissue following 8, 20 and 28 days amyloid-β1-40/amyloid-β1-42 intracerebroventricular infusion and sphingomyelinase activation after 8 and 28 days.