The role of the N-methyl-D-aspartate receptor in the proliferation of adult hippocampal neural stem and precursor cells  

作　　者：TAYLOR Chanel J HE RongQiao BARTLETT Perry F 

机构地区：[1]Queensland Brain Institute, The University of Queensland,Brisbane [2]Institute of Biophysics,Chinese Academy of Sciences

出　　处：《Science China(Life Sciences)》2014年第4期403-411,共9页中国科学（生命科学英文版）

摘　　要：New neurons are continuously generated from resident pools of neural stem and precursor cells(NSPCs)in the adult brain.There are multiple pathways through which adult neurogenesis is regulated,and here we review the role of the N-methyl-D-aspartate receptor(NMDAR)in regulating the proliferation of NSPCs in the adult hippocampus.Hippocampal-dependent learning tasks,enriched environments,running,and activity-dependent synaptic plasticity,all potently up-regulate hippocampal NSPC proliferation.We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity,and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons.We address how specific NMDAR agonists and antagonists modulate proliferation,both in vivo and in vitro,and then review the evidence supporting the hypothesis that NMDARs are present on NSPCs.We believe it is important to understand the mechanisms underlying the activation of adult neurogenesis,given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons.In conditions such as age-related memory decline,neurodegeneration and psychiatric disease,mature neurons are lost or become defective;as such,stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions.New neurons are continuously generated from resident pools of neural stem and precursor cells （NSPCs） in the adult brain. There are multiple pathways through which adult neurogenesis is regulated, and here we review the role of the N-methyl-D-aspartate receptor （NMDAR） in regulating the proliferation of NSPCs in the adult hippocampus. Hippocam- pal-dependent learning tasks, enriched environments, running, and activity-dependent synaptic plasticity, all potently up-regulate hippocampal NSPC proliferation. We first consider the requirement of the NMDAR in activity-dependent synaptic plasticity, and the role the induction of synaptic plasticity has in regulating NSPCs and newborn neurons. We address how specific NMDAR agonists and antagonists modulate proliferation, both in vivo and in vitro, and then review the evidence sup- porting the hypothesis that NMDARs are present on NSPCs. We believe it is important to understand the mechanisms under- lying the activation of adult neurogenesis, given the potential that endogenous stem cell populations have for repopulating the hippocampus with functional new neurons. In conditions such as age-related memory decline, neurodegeneration and psychia- tric disease, mature neurons are lost or become defective; as such, stimulating adult neurogenesis may provide a therapeutic strategy to overcome these conditions.

关 键 词：adult neurogenesis stem cell precursor cell NMDA receptor HIPPOCAMPUS synaptic plasticity long-term potentiation（LTP） 

分 类 号：R338[医药卫生—人体生理学]