Neural Regeneration Research ›› 2013, Vol. 8 ›› Issue (1): 49-55.doi: 10.3969/j.issn.1673-5374.2013.01.006

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Chronic pre-treatment with memantine prevents amyloid-beta protein-mediated long-term potentiation disruption

Fushun Li1, Xiaowei Chen1, Feiming Wang2, Shujun Xu1, Lan Chang1, Roger Anwyl3,    Qinwen Wang1
  

  1. 1 Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China
    2 Zhenhai High School, Ningbo 315211, Zhejiang Province, China
    3 Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland
  • Received:2012-07-01 Revised:2012-10-10 Online:2013-01-05 Published:2013-01-05
  • Contact: Qinwen Wang, Ph.D., Professor, Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China, wangqinwen@nbu.edu.cn.
  • About author:Fushun Li★, Master.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81070873, 30970932; Ningbo Natural Science Foundation, No. 2011A610065, 2010A610072, 2011A610064, 2011C51006; and the Scientific Research Fund of Zhejiang Provincial Education Department, No. Y201018164.

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Abstract:

Previous studies indicate that memantine, a low-affinity N-methyl-D-aspartate receptor antagonist, exerted acute protective effects against amyloid-β protein-induced neurotoxicity. In the present study, the chronic effects and mechanisms of memantine were investigated further using electrophysiological methods. The results showed that 7-day intraperitoneal application of memantine, at doses of 5 mg/kg or 20 mg/kg, did not alter hippocampal long-term potentiation induction in rats, while 40 mg/kg memantine presented potent long-term potentiation inhibition. Then further in vitro studys were carried out in 5 mg/kg and 20 mg/kg memantine treated rats. We found that 20 mg/kg memantine attenuated the potent long-term potentiation inhibition caused by exposure to amyloid-β protein in the dentate gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-β protein triggered long-term potentiation inhibition to improve synaptic plasticity.

Key words: neural regeneration, neurodegenerative diseases, memantine, amyloid-&beta, protein, long-term potentiation, synaptic plasticity, N-methyl-D-aspartate receptor, Alzheimer’s disease, hippocampus, grants-supported paper, neuroregeneration