Long-term treatment of l-3-n-butylphthalide attenuated neurodegenerative changes in aged rats.
It is shown that l-3-n-butylphthalide (l-NBP), the isomer of dl-NBP (racemic 3-n-butylphthalide, a new anti-cerebral ischemic agent) significantly attenuated cerebral hypoperfusion-induced learning dysfunction and brain damage in rats. In the present study, l-NBP (10 and 30 mg/kg) long-term (3-month) treatment of aged rat (21-month-old) significantly improved the learning and memory capability measured by the Morris water maze test. Hematoxylin-eosin-stained slices showed that both l-NBP at 30 mg/kg, and memantine as control at 20 mg/kg, attenuated the neurodegenerative changes in aged rats. L: -NBP treatment significantly increased the choline acetyltransferase activity and dose-dependently decreased the acetylcholinesterases activity in the hippocampus of aged rats. The immunohistological study demonstrated that expressions of beta-secretase and hyperphosphorylated tau protein were significantly increased in the hippocampus CA1 subfield and parietal cortex in aged rats. However, they were decreased significantly by treatment of l-NBP and memantine for 3 months. Our results indicated that long-term treatment with l-NBP might prevent age-related neurodegenerative changes by modulation of cholinergic system, reduction of phosphorylated tau and maintain structure and morphology of neurons. Therefore, l-NBP might be a potential drug for treatment of senile dementia.
Ma
Shiping
S
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China.
Xu
Shaofeng
S
Liu
Bin
B
Li
Jiang
J
Feng
Nan
N
Wang
Ling
L
Wang
Xiaoliang
X
D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D001572:Benzofurans; C027125:3-n-butylphthalide