Neuritin Enhances Synaptic Transmission in Medial Prefrontal Cortex in Mice by Increasing CaV3.3 Surface Expression
Neuritin Enhances Synaptic Transmission in Medial Prefrontal Cortex in Mice by Increasing CaV3.3 Surface Expression
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Neuritin 通过增加 CaV3.3 表面表达来增强小鼠内侧前额叶皮层的突触传递
DOI：
10.1093/cercor/bhx082
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发表时间：
2017-07-01
期刊：
影响因子：
3.7
通讯作者：
Mei, Yan-Ai
中科院分区：
文献类型：
--
作者：
Lu, Jun-Mei;Liu, Dong-Dong;Mei, Yan-Ai
神经蛋白是一种参与神经发育和突触可塑性的神经营养因子。然而，其在调节突触传递中的作用仍不清楚。在这里，我们研究了神经突蛋白对小鼠内侧前额皮质 (mPFC) 的微型兴奋性突触后电流 (mEPSC) 和谷氨酸释放的影响。通过高效液相色谱法测量，mPFC 切片与神经突蛋白一起孵育 45 分钟显着增加了 mEPSC 频率和谷氨酸释放，胰岛素可以模拟这种情况，但可以被胰岛素受体 (IR) 抑制剂消除。神经突触蛋白诱导的突触传递上调与 ERK 的激活相关，抑制丝裂原激活蛋白激酶/细胞外信号调节激酶 (MEK/ERK) 活性可减弱神经突蛋白诱导的 mEPSC 频率和谷氨酸释放的增加。 T 型钙通道抑制剂而非 L 型抑制剂消除了内向钙电流以及神经突蛋白对 mEPSC 频率和谷氨酸释放的影响。膜蛋白的蛋白质印迹显示神经突蛋白促进 CaV3.3 α 亚基的表面表达，这种表达也可以通过抑制 IR 或 MEK/ERK 活性而消除。神经突蛋白对 mEPSC 频率、谷氨酸释放和 CaV3.3 α 亚基表达的影响被细胞内蛋白转运抑制剂抑制。这些结果证实了 IR 和 ERK 信号通路的参与，并为突触传递中神经突蛋白功能的机制提供了新的见解。
Neuritin is a neurotrophic factor involved in neural development and synaptic plasticity. However, its role in modulating synaptic transmission remains unclear. Here, we investigated the effects of neuritin on miniature excitatory postsynaptic currents (mEPSCs) and glutamate release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with neuritin for 45 min significantly increased mEPSC frequency and glutamate release as measured by high-performance liquid chromatography, which was mimicked by insulin and abrogated by an insulin receptor (IR) inhibitor. Neuritin-induced upregulation of synaptic transmission was correlated with activation of ERK, and inhibition of mitogen-activated protein kinases/extracellular signal-regulated kinases (MEK/ERK) activity attenuated the neuritin-induced increase in mEPSC frequency and glutamate release. T-type calcium channel inhibitors but not the L-type inhibitor abolished the inward calcium current and the effects of neuritin on mEPSC frequency and glutamate release. Western blotting of membrane proteins showed that neuritin promoted surface expression of CaV3.3 α-subunit, which was also eliminated by inhibition of IR or MEK/ERK activity. The effects of neuritin on mEPSC frequency, glutamate release, and CaV3.3 α-subunit expression were inhibited by an intracellular protein-transport inhibitor. These results confirm involvement of the IR and ERK signaling pathway, and provide novel insights into the mechanisms of neuritin function in synaptic transmission.