Huperzine A attenuates cognitive dysfunction and neuronal degeneration caused by beta-amyloid protein-(1-40) in rat

Huperzine A, a promising therapeutic agent for Alzheimer's disease, was exa mined for its potential to antagonize the deleterious neurochemical, struct ural, and cognitive effects of infusing beta -amyloid protein-(1-40) into t he cerebral ventricles of rats. Daily intraperitoneal administration of hup erzine A for 12 consecutive days produced significant reversals of the beta -amyloid-induced deficit in learning a water maze task. This treatment als o reduced the loss of choline acetyltransferase activity in cerebral cortex , and the neuronal degeneration induced by beta -amyloid protein-(1-40). In addition, huperzine A partly reversed the down-regulation of anti-apoptoti c Bcl-2 and the up-regulation of pro-apoptotic Bar and P53 proteins and red uced the apoptosis that normally followed beta -amyloid injection. The pres ent findings confirm that huperzine A can alleviate the cognitive dysfuncti on induced by intracerebroventricular infusion of beta -amyloid protein-(1- 40) in rats. The beneficial effects are not confined to the cholinergic sys tem, but also include favorable changes in the expression of apoptosis-rela ted proteins and in the extent of apoptosis in widespread regions of the br ain. (C) 2001 Elsevier Science B.V. All rights reserved.