雌激素和Glu-NMDA受体通路与学习记忆相关性的研究进展

雌激素（estrogen,E）是维持女性第二性征最主要的甾体物质,其在神经系统也发挥广泛的药理作用,如抗脑缺血再灌注损伤减少梗死面积,抗自由基形成,调节兴奋性氨基酸释放等.雌激素自身作为一种抗氧化剂能够通过调节体内氧化还原平衡发挥神经保护作用.另外,雌激素在神经系统药理作用的发挥与其受体密不可分,经典的雌激素受体（estrogen receptor, ER）主要位于细胞核内,包括ER-α和ER-β两种亚型,二者均可在大脑皮质和海马表达：卵巢切除大鼠学习记忆能力降低的同时,ER-α在大脑皮质区和海马区表达也显著减少;ER-β基因敲除能够严重影响学习记忆行为、长时程增强（long term potentiation,LTP）和突触强度,该受体可能参与了高级脑功能的调节.N-甲基-D-天冬氨酸（N-methyl-D-aspartic acid,NMDA）受体作为与学习记忆密切相关的受体,与雌激素受体在海马区存在共表达.雌激素可能通过膜相关的雌激素受体快速激活ERK1/2信号转导通路,进一步诱导NMDA受体NR2B亚基磷酸化,激活NMDA受体,三者均会影响突触可塑性.本文就雌激素及其受体和Glu-NMDA受体通路与学习记忆的相关性进行综述.

Progress in Understanding the Relevance of Learning and Memory to Estrogen and Glu-NMDA Receptor Pathway

Besides maintaining the female secondary sexual characteristics, estrogen also plays important roles in the nervous system, especially in the brain： it can protect tissue from cerebral ischemia reperfusion injury and reduce infarct area by suppressing free radical formation, and can also regulate the release of excitatory amino acids. As an antioxidant, estrogen can protect the nervous system by regulating the body’s redox homeostasis. In addition, estrogen can play its neuroprotective role through estrogen receptors （ER）. ER-αand ER-β, two typical ER subtypes that are mainly located in the nucleus, are both expressed in the cerebral cortex and hippocampus. It has been found that ER-αlevel in the cortex and hippocampus of ovariectomized rats is decreased accompanying decreased learning and memory. LTP, synaptic density and learning and memory are all affected in ER-βgene knock-out mice. NMDA receptor is critical in learning and memory and is coexpressed in hippocampus with estrogen receptors. Estrogen may activate ERK1/2 signal transduction pathway through membrane estrogen receptors, thus inducing the phosphorylation of the NR2B subunit of NMDA receptor to activate NMDA receptor. In addition, the synaptic plasticity can be affected by estrogen and its receptors, as well as by NMDA receptor.