Lrp4 in astrocytes modulates glutamatergic transmission.
Lrp4 in astrocytes modulates glutamatergic transmission.
复制标题
星形胶质细胞中的 Lrp4 调节谷氨酸能传递
DOI：
10.1038/nn.4326
复制
发表时间：
2016-08
影响因子：
25
通讯作者：
Mei L
中科院分区：
文献类型：
--
作者：
Sun XD;Li L;Liu F;Huang ZH;Bean JC;Jiao HF;Barik A;Kim SM;Wu H;Shen C;Tian Y;Lin TW;Bates R;Sathyamurthy A;Chen YJ;Yin DM;Xiong L;Lin HP;Hu JX;Li BM;Gao TM;Xiong WC;Mei L
神经传递需要精确控制轴突末梢神经递质的释放。这一过程是由神经胶质细胞调节的;然而，其潜在机制尚未完全了解。我们发现，在缺乏低密度脂蛋白受体相关蛋白4（Lrp 4）的小鼠中，大脑中谷氨酸的释放受损，Lrp 4是一种对神经肌肉接头形成至关重要的蛋白质。电生理研究显示，Lrp 4基因敲除小鼠的ATP释放能力降低，Lrp 4基因突变小鼠的海马ATP水平升高，从而抑制了ATP的释放。因此，突变小鼠的自发活动和空间记忆受损，并且对癫痫诱导具有抗性。这些损伤可以通过阻断腺苷A1受体来改善。这些结果揭示了Lrp 4响应聚集蛋白在调节星形胶质细胞ATP释放和突触传递中的关键作用。我们的研究结果提供了深入了解神经元和星形胶质细胞之间的相互作用，突触稳态和/或可塑性。
Neurotransmission requires precise control of neurotransmitter release from axon terminals. This process is regulated by glial cells; however, the underlying mechanisms are not fully understood. We found that glutamate release in the brain was impaired in mice lacking low-density lipoprotein receptor–related protein 4 (Lrp4), a protein that is critical for neuromuscular junction formation. Electrophysiological studies revealed compromised release probability in astrocyte-specificLrp4knockout mice.Lrp4mutant astrocytes suppressed glutamatergic transmission by enhancing the release of ATP, whose level was elevated in the hippocampus ofLrp4mutant mice. Consequently, the mutant mice were impaired in locomotor activity and spatial memory and were resistant to seizure induction. These impairments could be ameliorated by blocking the adenosine A1 receptor. The results reveal a critical role for Lrp4, in response to agrin, in modulating astrocytic ATP release and synaptic transmission. Our findings provide insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.