title: Chronic pre-treatment with memantine prevents amyloid-beta protein-mediated long-term potentiation disruption.
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.
authors.affiliation: Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China.
authors.forename: Fushun
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Zhenhai High School, Ningbo 315211, Zhejiang Province, China.
authors.forename: Feiming
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China.
authors.forename: Shujun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chang
authors.affiliation: Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin, Ireland.
authors.forename: Roger
authors.initials: R
authors.lastname: Anwyl
authors.affiliation: Department of Physiology, Medical School, Research Center of Behavioral Science, Ningbo University, Ningbo 315211, Zhejiang Province, China.
authors.forename: Qinwen
authors.initials: Q
authors.lastname: Wang
keywords: Alzheimer's disease; N-methyl-D-aspartate receptor; amyloid-β protein; grants-supported paper; hippocampus; long-term potentiation; memantine; neural regeneration; neurodegenerative diseases; neuroregeneration; synaptic plasticity