Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance
Inhibition of phosphodiesterase 2 increases neuronal cGMP, synaptic plasticity and memory performance
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DOI：
10.1016/j.neuropharm.2004.07.040
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发表时间：
2004-12-01
影响因子：
4.7
通讯作者：
Koenig, G
中科院分区：
文献类型：
--
作者：
Boess, FG;Hendrix, M;Koenig, G
细胞内第二信使分子鸟苷3‘，5’-环一磷酸(CGMP)是导致突触可塑性的信号级联反应的重要元件。使用新的、有效的和选择性的抑制剂Bay 60-7550，我们证明了酶3‘，5’-环核苷酸磷酸二酯酶2(PDE2)负责在培养的神经元和海马片中降解新合成的cGMP。抑制PDE2可增强突触传递的长时程增强，而不改变基础突触传递。抑制PDE2还改善了大鼠在社会和物体识别记忆任务中的表现，并逆转了MK801诱导的小鼠在T迷宫中自发交替的缺陷。我们的数据提供了强有力的证据表明，抑制PDE2可以通过增强神经元的可塑性来改善记忆功能。(C)2004爱思唯尔有限公司。保留所有权利。
An essential element of the signalling cascade leading to synaptic plasticity is the intracellular second messenger molecule guanosine 3',5'-cyclic monophosphate (cGMP). Using the novel, potent, and selective inhibitor Bay 60-7550, we show that the enzyme 3',5'-cyclic nucleotide phosphodiesterase type 2 (PDE2) is responsible for the degradation of newly synthesized cGMP in cultured neurons and hippocampal slices. Inhibition of PDE2 enhanced long-term potentiation of synaptic transmission without altering basal synaptic transmission. Inhibition of PDE2 also improved the performance of rats in social and object recognition memory tasks, and reversed MK801-induced deficits in spontaneous alternation in mice in a T-maze. Our data provide strong evidence that inhibition of PDE2 can improve memory functions by enhancing neuronal plasticity. (C) 2004 Elsevier Ltd. All rights reserved.