The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission
The Endocannabinoid 2-Arachidonoylglycerol Produced by Diacylglycerol Lipase α Mediates Retrograde Suppression of Synaptic Transmission
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DOI：
10.1016/j.neuron.2010.01.021
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发表时间：
2010-02-11
期刊：
影响因子：
16.2
通讯作者：
Kano, Masanobu
中科院分区：
文献类型：
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作者：
Tanimura, Asami;Yamazaki, Maya;Kano, Masanobu
内源性大麻素从突触后神经元释放并引起突触传递的逆行抑制。Anandamide和2-花生四烯醇甘油（2-AG）被认为是两种主要的内源性大麻素。为了确定2-AG在多大程度上有助于逆行信号传导，我们生成并分析了缺乏两种2-AG合成酶二酰基甘油脂肪酶α (DGL α)和β (DGL β)中的一种的突变小鼠。我们发现，在DGL α敲除小鼠的小脑、海马和纹状体中，内源性大麻素介导的逆行突触抑制完全不存在，而在DGL β敲除小鼠的大脑中，逆行抑制是完整的。DGL α敲除脑组织中2-AG的基础含量明显降低，刺激诱导的2-AG升高不存在，而DGL β敲除脑组织中2-AG含量正常。在两个基因敲除小鼠中，脑形态和产生2-AG所需分子的表达正常，而不是DGLs。我们得出结论，由DGL α产生的2-AG介导中枢突触的逆行抑制，而不是由DGL β产生的。
Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGL alpha) and beta (DGL beta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGL alpha knockout mice, whereas the retrograde suppression was intact in DGL beta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGL alpha knockout brains, whereas the 2-AG content was normal in DGL beta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGL alpha, but not by DGL beta, mediates retrograde suppression at central synapses.