amyloid-beta-peptides and 3-n-butylphthalide

To determine the expression of S100-beta protein and glial fibrillary acidic protein (GFAP) in hippocampal astrocytes of rats with Alzheimer disease (AD) model rats, and observe the effect of butylphthalide on their expression.. Sixty male adult rats were randomized equally into model group, butylphthalide group, and control group, and in the former two groups, AD models were established by injecting beta-amyloid protein 1-40 into the hippocampus. Sixty days later, the rats were sacrificed and the bilateral hippocampuses were taken for immunohistochemistry.. The number of cells positive for S100 and GFAP in the hippocampus in butylphthalide group were significantly higher than that in the control group (P/0.01), but lower than that in the model group (P/0.05).. The expression of S100 protein and glial fibrillary acidic protein increased significantly in the hippocampal astrocytes of rats with AD, and butylphthalide can inhibit the increase of their expression.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Benzofurans; Disease Models, Animal; Glial Fibrillary Acidic Protein; Hippocampus; Male; Nerve Growth Factors; Neuroprotective Agents; Peptide Fragments; Random Allocation; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein beta Subunit; S100 Proteins

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.

Topics: Amyloid beta-Peptides; Animals; Apoptosis; Benzofurans; Cerebral Ventricles; Cognition Disorders; Infusion Pumps; Learning; Male; Memory; Neurons; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Phosphorylation; Rats; Rats, Wistar; tau Proteins