L-3-n-butylphthalide improves cognitive impairment induced by intracerebroventricular infusion of amyloid-beta peptide in rats.

Abstract

Alzheimer's disease is the most common form of dementia. Amyloid-beta protein is considered as a key factor of pathogenesis of Alzheimer's disease. l-3-n-butylphthalide (L-NBP), an anti-cerebral ischemia drug, has been shown to have therapeutic effects in vascular dementia animal models. In the present study, we investigated the potential of L-NBP to protect against cognitive impairment, oxidative damage and neuropathological changes induced by intracerebroventricular infusion of amyloid-beta peptide in rats. Daily treatments of 10 and 30 mg/kg L-NBP significantly improved spatial learning deficits and attenuated working memory deficits in Morris water maze task. L-NBP partially reversed the reduction of glutathione peroxidase activities and decreased malondialdehyde levels in the cortex and hippocampus. Furthermore, L-NBP markedly inhibited amyloid-beta-induced neuronal apoptosis, possibly by blocking caspase-3 activation. In addition, L-NBP reduced activation of glycogen synthase kinase-3beta and tau protein phosphorylation. Our results demonstrate that L-NBP protects against amyloid-beta-induced neurodegeneration and cognitive decline in a rat model, suggesting that it may have potential as a therapy for Alzheimer's disease.

• Authors: Ying Peng, Changhong Xing, Shaofeng Xu, Cynthia A Lemere, Guiquan Chen, Bin Liu, Ling Wang, Yipu Feng, Xiaoliang Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 621 Issue 1-3 Pg. 38-45 (Oct 25 2009) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 19737553 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Benzofurans
• Neuroprotective Agents
• Peptide Fragments
• amyloid beta-protein (1-40)
• tau Proteins
• 3-n-butylphthalide

Topics

• Amyloid beta-Peptides (administration & dosage, pharmacology)
• Animals
• Apoptosis (drug effects)
• Benzofurans (pharmacology, therapeutic use)
• Cerebral Ventricles
• Cognition Disorders (chemically induced, drug therapy, pathology, physiopathology)
• Infusion Pumps
• Learning (drug effects)
• Male
• Memory (drug effects)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Peptide Fragments (administration & dosage, pharmacology)
• Phosphorylation (drug effects)
• Rats
• Rats, Wistar
• tau Proteins (metabolism)