Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior
Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior
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DOI：
10.1038/mp.2008.130
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发表时间：
2009-07-01
影响因子：
11
通讯作者：
Coyle, J. T.
中科院分区：
文献类型：
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作者：
Basu, A. C.;Tsai, G. E.;Coyle, J. T.
对谷氨酸类似物N-甲基-D-天冬氨酸（NMDA）特别敏感的谷氨酸受体的一个子集是分子符合检测器，对于神经发育的活动依赖性过程以及感觉和认知功能是必需的。这些受体的活性由内源性氨基酸D-丝氨酸调节，但D-丝氨酸对哺乳动物神经系统的正常发育和功能所必需的程度以前是未知的。基于药理学证据，NMDA受体的信号传导减少与精神分裂症的病理生理学有关，并且与D-丝氨酸代谢和谷氨酸能神经传递相关的几种人类基因与精神分裂症的病因学有关。在这里，我们表明，缺乏内源性产生D-丝氨酸的能力的转基因小鼠已经深刻地改变了多巴胺能神经传递，以及反映多动和空间记忆受损的相对微妙但显著的行为异常，并且与焦虑升高一致。Molecular Psychiatry（2009）14，719-727; doi：10.1038/mp.2008.130; 2008年12月9日在线发表
A subset of glutamate receptors that are specifically sensitive to the glutamate analog N-methyl-D-aspartate (NMDA) are molecular coincidence detectors, necessary for activity-dependent processes of neurodevelopment and in sensory and cognitive functions. The activity of these receptors is modulated by the endogenous amino acid D-serine, but the extent to which D-serine is necessary for the normal development and function of the mammalian nervous system was previously unknown. Decreased signaling at NMDA receptors has been implicated in the pathophysiology of schizophrenia based on pharmacological evidence, and several human genes related to D-serine metabolism and glutamatergic neurotransmission have been implicated in the etiology of schizophrenia. Here we show that genetically modified mice lacking the ability to produce D-serine endogenously have profoundly altered glutamatergic neurotransmission, and relatively subtle but significant behavioral abnormalities that reflect hyperactivity and impaired spatial memory, and that are consistent with elevated anxiety. Molecular Psychiatry (2009) 14, 719-727; doi:10.1038/mp.2008.130; published online 9 December 2008