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Long-term treatment of l-3-n-butylphthalide attenuated neurodegenerative changes in aged rats

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Abstract

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 β-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.

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Acknowledgements

We appreciate Dr. Song Wu for the supply of memantine. We thank Mrs. Li Zhang and Xiping Chen for their technical help.

This work was supported by the National 973 Fundamental Project of China (no. 2004CB518906); National Natural Science Foundation of China (no. 30640096); Program for Changjiang Scholars and Innovative Research Team in University (no. IRT0514); and Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xian Nong Tan Street, Beijing, 100050, China

    Shiping Ma, Shaofeng Xu, Bin Liu, Jiang Li, Nan Feng, Ling Wang & Xiaoliang Wang

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  1. Shiping Ma
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  2. Shaofeng Xu
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Correspondence to Xiaoliang Wang.

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Ma, S., Xu, S., Liu, B. et al. Long-term treatment of l-3-n-butylphthalide attenuated neurodegenerative changes in aged rats. Naunyn-Schmied Arch Pharmacol 379, 565–574 (2009). https://doi.org/10.1007/s00210-009-0398-8

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