Memory defect induced by β-amyloid plus glutamate receptor agonist is alleviated by catalpol and donepezil through different mechanisms.

Zhiming Xia, Rui Zhang, Pingping Wu, Zongqin Xia, Yaer Hu

Research Laboratory of Cell Regulation, Shanghai Jiaotong University Medical School, 280 South Chongqing Road, Shanghai 200025, China.

Brain research 2012 Mar 2

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Our previous studies demonstrate that a non-cholinesterase inhibitor (AChEI) compound catalpol, purified from a traditional Chinese medicinal herb Rehmannia glutinosa, could improve the symptoms and pathological changes in animal and cellular models of memory related neurodegenerative diseases. In this study, we compared catalpol with the most commonly used AChEI donepezil in respect to their mechanism of action on the neurodegenerative changes in an animal model induced by beta-amyloid (Aβ) plus glutamate receptor agonist. It was found that the model mice showed significant deficit in the learning ability and memory in Y maze avoidance test, and meanwhile both donepezil and catalpol greatly improve the learning ability and memory after 2 to 3 months' administration. At the selected doses, donepezil only partially raised the declined brain muscarinic acetylcholine receptor (M receptor) density and choline acetyltransferase (ChAT) activity resulting in these levels still lower than normal control, while catalpol completely retrieved these two parameters. ELISA revealed that catalpol, instead of donepezil, possessed the capability of elevating the declined brain BDNF level of the animal model. The ELISA results on the BDNF protein level was confirmed by quantitative RT-PCR measurement of BDNF mRNA in Aβ₂₅₋₃₅-treated primary culture of forebrain neurons. In combination with our previous work, we think the neuroprotective effects of donepezil and catalpol are mediated through different mechanisms. Since BDNF has been proved to be an important intrinsic factor in protecting neurodegenerative diseases, catalpol may be a hopefully effective compound against neurodegenerative changes induced by Aβ and glutamate receptor agonist. Crown Copyright Â© 2012. Published by Elsevier B.V. All rights reserved.

Citation

Zhiming Xia, Rui Zhang, Pingping Wu, Zongqin Xia, Yaer Hu. Memory defect induced by β-amyloid plus glutamate receptor agonist is alleviated by catalpol and donepezil through different mechanisms. Brain research. 2012 Mar 2;1441:27-37