Activation of metabotropic glutamate receptor 4 regulates proliferation and neural differentiation in neural stem/progenitor cells of the rat subventricular zone and increases phosphatase and tensin homolog protein expression
Activation of metabotropic glutamate receptor 4 regulates proliferation and neural differentiation in neural stem/progenitor cells of the rat subventricular zone and increases phosphatase and tensin homolog protein expression
复制标题
代谢型谷氨酸受体 4 的激活调节大鼠室下区神经干/祖细胞的增殖和神经分化，并增加磷酸酶和张力蛋白同源蛋白的表达
DOI：
10.1111/jnc.14984
复制
发表时间：
2020-02
影响因子：
4.7
通讯作者：
Liu Yong
中科院分区：
文献类型：
--
作者：
Zhang Zhichao;Zheng Xiaoyan;Liu Yingfei;Luan Yan;Wang Li;Zhao Lingyu;Zhang Jianshui;Tian Yumei;Lu Haixia;Chen Xinlin;Liu Yong
神经干/祖细胞（neural stem/progenitor cells，NSPCs）在哺乳动物的脑室下区（subventricular zone）终生存在，在生理和病理生理刺激下被激活。最近的研究表明代谢型谷氨酸受体4（mGluR 4）参与调节NSPCs的行为。因此，确定mGluR 4在NSPCs中的功能对于确定新的策略以增强损伤后脑再生的内在潜力是必要的。在本研究中，mGluR 4在来自雄性Sprague-道利大鼠的SVZ衍生的NSPCs中功能性表达，其中在用mGluR 4特异性激动剂VU 0155041处理后，环磷酸腺苷浓度降低。此外，侧脑室注射VU 0155041显著减少SVZ中的5-溴-2 '-脱氧尿苷（BrdU）+和Ki 67+细胞，同时增加Doublecortin（DCX）/BrdU双阳性细胞。在培养的NSPCs中，mGluR 4活化降低BrdU+细胞、G2/M期细胞的比例，并抑制Cyclin D1表达，而增加神经元特异性III类β微管蛋白（Tuj 1）表达和Tuj 1、DCX和PSA-NCAM阳性细胞的数量。然而，药理学阻断mGluR 4与拮抗剂MSOP或敲低mGluR 4废除VU 0155041对NSPCs增殖和神经元分化的影响。进一步的研究表明，VU 0155041处理在NSPCs培养物中下调AKT磷酸化并上调磷酸酶和张力蛋白同源蛋白（PTEN）的表达。此外，VU 0155041诱导的NSPCs中的增殖抑制和神经元分化扩增被V0-OHpic（一种PTEN抑制剂）显著阻碍。我们得出结论，SVZ衍生的NSPCs中mGluR 4的激活抑制增殖并增强其神经元分化，并且PTEN的调节可能作为mGluR 4信号的潜在细胞内靶点而参与。
Neural stem/progenitor cells (NSPCs) persist in the mammalian subventricular zone throughout life, where they can be activated in response to physiological and pathophysiological stimuli. A recent study indicates metabotropic glutamate receptor 4 (mGluR4) is involved in regulating NSPCs behaviors. Therefore, defining mGluR4 function in NSPCs is necessary for determining novel strategies to enhance the intrinsic potential for brain regeneration after injuries. In this study, mGluR4 was functionally expressed in SVZ‐derived NSPCs from male Sprague‐Dawley rats, in which the cyclic adenosine monophosphate concentration was reduced after treatment with the mGluR4‐specific agonist VU0155041. Additionally, lateral ventricle injection of VU0155041 significantly decreased 5‐bromo‐2'‐deoxyuridine (BrdU)+ and Ki67+ cells, while increased Doublecortin (DCX)/BrdU double‐positive cells in SVZ. In cultured NSPCs, mGluR4 activation decreased the ratio of BrdU+ cells, G2/M‐phase cells, and inhibited Cyclin D1 expression, whereas it increased neuron‐specific class III β‐tubulin (Tuj1) expression and the number of Tuj1, DCX, and PSA‐NCAM‐positive cells. However, pharmacological blocking mGluR4 with the antagonist MSOP or knockdown of mGluR4 abolished the effects of VU0155041 on NSPCs proliferation and neuronal differentiation. Further investigation demonstrated that VU0155041 treatment down‐regulated AKT phosphorylation and up‐regulated expression of the phosphatase and tensin homolog protein (PTEN) in NSPCs culture. Moreover VU0155041‐induced proliferating inhibition and neuronal differentiating amplification in NSPCs were significantly hampered by VO‐OHpic, a PTEN inhibitor. We conclude that activation of mGluR4 in SVZ‐derived NSPCs suppresses proliferation and enhances their neuronal differentiation, and regulation of PTEN may be involved as a potential intracellular target of mGluR4 signal.
登录
查看更多内容
影响因子：
62.1
作者：
Lindsley CW;Emmitte KA;Hopkins CR;Bridges TM;Gregory KJ;Niswender CM;Conn PJ
通讯作者：
Conn PJ
影响因子：
64.8
作者：
Zheng, Hongwu;Ying, Haoqiang;Yan, Haiyan;Kimmelman, Alec C.;Hiller, David J.;Chen, An-Jou;Perry, Samuel R.;Tonon, Giovanni;Chu, Gerald C.;Ding, Zhihu;Stommel, Jayne M.;Dunn, Katherine L.;Wiedemeyer, Ruprecht;You, Mingjian J.;Brennan, Cameron;Wang, Y. Alan;Ligon, Keith L.;Wong, Wing H.;Chin, Lynda;DePinho, Ronald A.
通讯作者：
DePinho, Ronald A.
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
影响因子：
4.3
作者：
Sierra A;Encinas JM;Maletic-Savatic M
通讯作者：
Maletic-Savatic M
DOI：
10.1124/jpet.107.124701
发表时间：
2007-10-01
影响因子：
3.5
作者：
Suzuki, Gentaroh;Tsukamoto, Naohiro;Ohta, Hisashi
通讯作者：
Ohta, Hisashi