L-3-n-butylphthalide improves cognitive impairment induced by intracerebroventricular infusion of amyloid-beta peptide in rats.
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.
Peng
Ying
Y
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Xuanwu District, Beijing, China.
Xing
Changhong
C
Xu
Shaofeng
S
Lemere
Cynthia A
CA
Chen
Guiquan
G
Liu
Bin
B
Wang
Ling
L
Feng
Yipu
Y
Wang
Xiaoliang
X
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology* / Q000627:therapeutic use; D002552:Cerebral Ventricles; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007260:Infusion Pumps; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001572:Benzofurans; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D016875:tau Proteins; C027125:3-n-butylphthalide