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Memantine ameliorates cognitive deficit in AD mice via enhancement of entorhinal-CA1 projection
Peng Li1, Jin Xu1, Huanhuan Gu1
1Department of Neurology, Shanghai Changzheng Hospital, Navy Medical University, Shanghai, 200003, China.
Background:
Memantine, a low- to moderate-affinity uncompetitive N-methyl-D-aspartate receptor antagonist, has been shown to improve cognitive functions in animal models of Alzheimer's disease (AD). Here we treated APP/PS1 AD mice with a therapeutic dose of memantine (20 mg/kg/day) and examined its underlying mechanisms in ameliorating cognitive defects.
Methods:
Using behavioral, electrophysiological, optogenetic and morphology approaches to explore how memantine delay the pathogenesis of AD.
Results:
Memantine significantly improved the acquisition in Morris water maze (MWM) in APP/PS1 mice without affecting the speed of swimming. Furthermore, memantine enhanced EC to CA1 synaptic neurotransmission and promoted dendritic spine regeneration of EC neurons that projected to CA1.
Conclusions:
Our study reveals the underlying mechanism of memantine in the treatment of AD mice.
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