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 examined for its potential to antagonize the deleterious neurochemical, structural, and cognitive effects of infusing beta-amyloid protein-(1-40) into the cerebral ventricles of rats. Daily intraperitoneal administration of huperzine A for 12 consecutive days produced significant reversals of the beta-amyloid-induced deficit in learning a water maze task. This treatment also 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-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax and P53 proteins and reduced the apoptosis that normally followed beta-amyloid injection. The present findings confirm that huperzine A can alleviate the cognitive dysfunction induced by intracerebroventricular infusion of beta-amyloid protein-(1-40) in rats. The beneficial effects are not confined to the cholinergic system, but also include favorable changes in the expression of apoptosis-related proteins and in the extent of apoptosis in widespread regions of the brain.
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State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, People's Republic of China.
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D000470:Alkaloids; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007260:Infusion Pumps; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000470:Alkaloids; D016229:Amyloid beta-Peptides; C494826:BAX protein, human; C494828:Bax protein, rat; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; C078592:amyloid beta-protein (1-40); D051028:bcl-2-Associated X Protein; C050426:huperzine A; D002795:Choline O-Acetyltransferase