Vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release and membrane GluA1 activation is involved in the rapid antidepressant-like effects of scopolamine in mice
Vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release and membrane GluA1 activation is involved in the rapid antidepressant-like effects of scopolamine in mice
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囊泡谷氨酸转运蛋白 1 (VGLUT1) 介导的谷氨酸释放和膜 GluA1 激活参与东莨菪碱对小鼠的快速抗抑郁样作用
DOI：
10.1016/j.neuropharm.2017.12.028
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发表时间：
2018-03
影响因子：
4.7
通讯作者：
Wang Chuang
中科院分区：
文献类型：
--
作者：
Yu Hanjie;Li Mengmeng;Zhou Dongsheng;Lv Dan;Liao Qi;Lou Zhongze;Shen Mengxin;Wang Zhen;Li Ming;Xiao Xiao;Zhang Yanhua;Wang Chuang
新出现的数据已确定某些药物（如东莨菪碱）可作为治疗重度抑郁症（MDD）的速效抗抑郁药，在啮齿动物模型中通过α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）激活增加谷氨酸释放并诱导神经营养因子。然而，很少有研究涉及东莨菪碱对AMPAR激活或囊泡谷氨酸转运体1（VGLUT 1）介导的小鼠前额叶皮层（PFC）谷氨酸释放的直接机制。在此，使用慢性不可预测的压力（CUS）范例，东莨菪碱急性治疗迅速逆转应激诱导的抑郁样行为的小鼠。结果表明，东莨菪碱诱导的小鼠抑郁样行为伴随着PFC膜AMPAR亚基1（GluA 1）、磷酸化GluA 1 Ser 845（pGluA 1 Ser 845）、脑源性神经营养因子（BDNF）和VGF（non-acronymic）的减少以及biccaudal C homolog 1基因（BICC 1）的增加，而这些生化和行为异常可被东莨菪碱急性处理所改善。然而，通过将NBQX输注到PFC中的AMPAR的药理学阻断显著地消除了东莨菪碱的这些作用。此外，在小鼠PFC中通过慢病毒介导的RNA干扰敲低VGLUT 1足以诱导抑郁样表型，减少细胞外谷氨酸积累，并引起与小鼠CUS相似的分子变化。值得注意的是，VGLUT 1敲低减轻了东莨菪碱的快速抗抑郁样作用和东莨菪碱对膜GluA 1介导的BDNF，VGF和BICC 1变化的影响。总之，我们的研究结果表明，VGLUT 1介导的谷氨酸释放和膜GluA 1激活可能在东莨菪碱在小鼠中的速效抗抑郁样作用中发挥关键作用。
Emerging data have identified certain drugs such as scopolamine as rapidly acting antidepressants for major depressive disorder (MDD) that increase glutamate release and induce neurotrophic factors through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation in rodent models. However, little research has addressed the direct mechanisms of scopolamine on AMPAR activation or vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release in the prefrontal cortex (PFC) of mice. Herein, using a chronic unpredictable stress (CUS) paradigm, acute treatment with scopolamine rapidly reversed stress-induced depression-like behaviors in mice. Our results showed that CUS-induced depression-like behaviors, accompanied by a decrease in membrane AMPAR subunit 1 (GluA1), phosphorylated GluA1 Ser845 (pGluA1 Ser845), brain-derived neurotrophic factor (BDNF) and VGF (non-acronymic) and an increase in bicaudal C homolog 1 gene (BICC1) in the PFC of mice, and these biochemical and behavioral abnormalities were ameliorated by acute scopolamine treatments. However, pharmacological block of AMPAR by NBQX infusion into the PFC significantly abolished these effects of scopolamine. In addition, knock down of VGLUT1 by lentiviral-mediated RNA interference in the PFC of mice was sufficient to induce depression-like phenotype, to decrease extracellular glutamate accumulation and to cause similar molecular changes with CUS in mice. Remarkably, VGLUT1 knockdown alleviated the rapid antidepressant-like actions of scopolamine and the effects of scopolamine on membrane GluA1-mediated BDNF, VGF and BICC1 changes. Altogether, our findings suggest that VGLUT1-mediated glutamate release and membrane GluA1 activation may play a critical role in the rapid-acting antidepressant-like effects of scopolamine in mice.
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影响因子：
11
作者：
Chowdhury GM;Zhang J;Thomas M;Banasr M;Ma X;Pittman B;Bristow L;Schaeffer E;Duman RS;Rothman DL;Behar KL;Sanacora G
通讯作者：
Sanacora G
影响因子：
4.6
作者：
Ma M;Ren Q;Yang C;Zhang JC;Yao W;Dong C;Ohgi Y;Futamura T;Hashimoto K
通讯作者：
Hashimoto K
影响因子：
34.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
DOI：
10.1523/jneurosci.3145-08.2008
发表时间：
2008-09-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bozdagi O;Rich E;Tronel S;Sadahiro M;Patterson K;Shapiro ML;Alberini CM;Huntley GW;Salton SR
通讯作者：
Salton SR
影响因子：
5.3
作者：
Jeon WJ;Dean B;Scarr E;Gibbons A
通讯作者：
Gibbons A