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

• 作 者: Fushun Li Xiaowei Chen Feiming Wang Shujun Xu Lan Chang Roger Anwyl Qinwen Wang
• 机 构: Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University,Z
• 出 处: Neural Regeneration Research
• 发表日期: 2013年01期
• 关键词: amyloid potentiation disruption hippocampal synaptic minutes protective dentate

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.

Previous studies indicate that memantine, a low-affinity N-methyl-D-aspartate receptor antagonist, exerted acute protective effects against amyloid-beta 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 denture gyrus in vitro. These findings are the first to demonstrate the antagonizing effect of long-term systematic treatment of memantine against amyloid-beta protein triggered long-term potentiation inhibi tion to improve synaptic plasticity.