Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone.
Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone.
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Alpha-7 烟碱受体信号通路参与室下区 ChAT 阳性神经元诱导的神经发生
DOI：
10.1007/s12975-017-0541-7
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发表时间：
2017-05-27
影响因子：
6.9
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Wang J;Lu Z;Fu X;Zhang D;Yu L;Li N;Gao Y;Liu X;Yin C;Ke J;Li L;Zhai M;Wu S;Fan J;Lv L;Liu J;Chen X;Yang Q;Wang J
室下区（SVZ）内胆碱乙酰转移酶阳性（ChAT+）神经元已被证明通过分泌乙酰胆碱（ACh）促进小鼠卒中后的神经发生;然而，其机制尚不清楚。已知结合ACh的受体包括烟碱型ACh受体（nAChR），其存在于SVZ中，并且已显示对细胞增殖、分化和存活重要。在本研究中，我们研究了α 7 nAChR（α7 nAChR）在大脑中动脉闭塞（MCAO）小鼠模型中的神经发生作用，通过使用α7 nAChR抑制剂甲基甘草次酸。接受MCAO的小鼠表现出细胞膜和核成纤维细胞生长因子受体1（FGFR 1）的表达升高，以及PI 3 K、pAkt、双皮质素（DCX）、多唾液酸化神经元细胞粘附分子（PSA-NCAM）和哺乳动物无毛细胞-鳞片同源物1（Mash 1）的表达升高。与假手术组相比，MCAO组SVZ内胶质细胞酸性蛋白（GFAP）/5-溴-2 ′-脱氧尿苷（BrdU）阳性细胞和DCX阳性细胞也增多。与溶剂处理的MCAO小鼠相比，甲基牛乌头碱处理增加了细胞膜FGFR 1表达和GFAP/BrdU阳性细胞，上调了磷酸肌醇3-激酶（PI 3 K）和磷酸化Akt（pAkt）的水平，降低了核FGFR 1表达，减少了DCX阳性细胞的数量，并降低了MCAO小鼠SVZ中DCX、PSA-NCAM和Mash 1的水平。接受α7 nAChR激动剂PNU-282987治疗的MCAO小鼠表现出相反的作用。我们的数据表明，α7 nAChR可能会降低神经干细胞的增殖，促进现有的神经干细胞分化后中风。这些结果确定了SVZ ChAT+神经元诱导神经发生的新机制。
Choline acetyltransferase-positive (ChAT+) neurons within the subventricular zone (SVZ) have been shown to promote neurogenesis after stroke in mice by secreting acetylcholine (ACh); however, the mechanisms remain unclear. Receptors known to bind ACh include the nicotinic ACh receptors (nAChRs), which are present in the SVZ and have been shown to be important for cell proliferation, differentiation, and survival. In this study, we investigated the neurogenic role of the alpha-7 nAChR (α7 nAChR) in a mouse model of middle cerebral artery occlusion (MCAO) by using α7 nAChR inhibitor methyllycaconitine. Mice subjected to MCAO exhibited elevated expression of cytomembrane and nuclear fibroblast growth factor receptor 1 (FGFR1), as well as increased expression of PI3K, pAkt, doublecortin (DCX), polysialylated - neuronal cell adhesion molecule (PSA-NCAM), and mammalian achaete-scute homolog 1 (Mash1). MCAO mice also had more glial fibrillary acidic protein (GFAP)/5-bromo-2′-deoxyuridine (BrdU)-positive cells and DCX-positive cells in the SVZ than did the sham-operated group. Methyllycaconitine treatment increased cytomembrane FGFR1 expression and GFAP/BrdU-positive cells, upregulated the levels of phosphoinositide 3-kinase (PI3K) and phospho-Akt (pAkt), decreased nuclear FGFR1 expression, decreased the number of DCX-positive cells, and reduced the levels of DCX, PSA-NCAM, and Mash1 in the SVZ of MCAO mice compared with levels in vehicle-treated MCAO mice. MCAO mice treated with α7 nAChR agonist PNU-282987 exhibited the opposite effects. Our data show that α7 nAChR may decrease the proliferation of neural stem cells and promote differentiation of existing neural stem cells after stroke. These results identify a new mechanism of SVZ ChAT+neuron-induced neurogenesis.
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影响因子：
3.7
作者：
Ji R;Meng L;Jiang X;Cvm NK;Ding J;Li Q;Lu Q
通讯作者：
Lu Q
DOI：
10.1073/pnas.1218991110
发表时间：
2013-03-19
影响因子：
11.1
作者：
Deshpande, Aditi;Bergami, Matteo;Berninger, Benedikt
通讯作者：
Berninger, Benedikt
影响因子：
6.9
作者：
Chang CF;Cai L;Wang J
通讯作者：
Wang J
DOI：
10.1016/j.bbi.2016.12.012
发表时间：
2017-03
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Lan X;Han X;Li Q;Li Q;Gao Y;Cheng T;Wan J;Zhu W;Wang J
通讯作者：
Wang J
DOI：
10.3791/50326
发表时间：
2013-05-12
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
DeVos SL;Miller TM
通讯作者：
Miller TM