Endothelium-Derived Semaphorin 3G Regulates Hippocampal Synaptic Structure and Plasticity via Neuropilin-2/PlexinA4
Endothelium-Derived Semaphorin 3G Regulates Hippocampal Synaptic Structure and Plasticity via Neuropilin-2/PlexinA4
复制标题
内皮源性信号蛋白 3G 通过 Neuropilin-2/PlexinA4 调节海马突触结构和可塑性
DOI：
10.1016/j.neuron.2018.12.036
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发表时间：
2019-03-06
期刊：
影响因子：
16.2
通讯作者：
Han, Feng
中科院分区：
文献类型：
--
作者：
Tan, Chao;Lu, Nan-Nan;Han, Feng
血管和神经元之间的适当相互作用对于维持神经回路和认知功能的强度至关重要。然而，这些相互作用背后的精确分子事件在很大程度上仍然未知。在这里，我们报告说，选择性敲除脑信号蛋白3G（Sema 3G）在内皮细胞受损的海马依赖性记忆和减少树突棘密度在小鼠CA 1神经元，这些影响被逆转后，恢复Sema 3G水平在海马通过AAV转染。我们进一步表明，Sema 3G增加兴奋性突触密度通过neuropilin-2/丛蛋白A4信号和通过激活Rac 1。这些结果提供了第一个证据表明，在中枢神经系统中，内皮细胞Sema 3G作为血管源性突触组织者，调节突触可塑性和突触依赖性记忆。我们的研究结果强调了血管内皮细胞通过与海马神经元的细胞间通讯在调节认知功能中的作用。
The proper interactions between blood vessels and neurons are critical for maintaining the strength of neural circuits and cognitive function. However, the precise molecular events underlying these interactions remain largely unknown. Here, we report that the selective knockout of semaphorin 3G (Sema3G) in endothelial cells impaired hippocampal-dependent memory and reduced dendritic spine density in CA1 neurons in mice; these effects were reversed after restoration of Sema3G levels in the hippocampus by AAV transfection. We further show that Sema3G increased excitatory synapse density via neuropilin-2/PlexinA4 signaling and through activation of Rac1. These results provide the first evidence that, in the central nervous system, endothelial Sema3G serves as a vascular-derived synaptic organizer that regulates synaptic plasticity and hippocampal-dependent memory. Our findings highlight the role of vascular endothelial cells in regulating cognitive function through intercellular communication with neurons in the hippocampus.