Beaumont Vahri, Thompson Sally-Anne, Choudhry Fahd, Nuthall Hugh, Glantschnig Helmut, Lipfert Lorraine, David Gabriela R, Swain Christopher J, McAllister George, Munoz-Sanjuan Ignacio
The Neuroscience Research Centre, Merck Sharp and Dohme, Terlings Park, Harlow Essex CM20 2QR, UK.
Mol Cell Neurosci. 2007 Aug;35(4):513-24. doi: 10.1016/j.mcn.2007.03.004. Epub 2007 Mar 14.
The role for Wnt signaling modulation during synaptogenesis, neurogenesis and cell fate specification have been well characterized. In contrast, the roles for Wnt signaling pathways in the regulation of synaptic plasticity and adult physiology are only starting to be elucidated. Here, we have identified a novel series of Wnt pathway small molecule modulators, and report that these and other small molecules targeting the Wnt pathway acutely enhance excitatory transmission in adult hippocampal preparations. Our findings are consistent with a pre- and postsynaptic site of action, leading to both increased spontaneous and evoked neurotransmission that occurs in a transcription-independent fashion.
Wnt信号调节在突触发生、神经发生和细胞命运特化过程中的作用已得到充分表征。相比之下，Wnt信号通路在调节突触可塑性和成年生理学中的作用才刚刚开始被阐明。在这里，我们鉴定出了一系列新型的Wnt通路小分子调节剂，并报告称这些以及其他靶向Wnt通路的小分子可急性增强成年海马制备物中的兴奋性传递。我们的发现与突触前和突触后作用位点一致，导致以转录非依赖方式发生的自发性和诱发性神经传递均增加。
