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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\u2010derived NSPCs from male Sprague\u2010Dawley rats, in which the cyclic adenosine monophosphate concentration was reduced after treatment with the mGluR4\u2010specific agonist VU0155041. Additionally, lateral ventricle injection of VU0155041 significantly decreased 5\u2010bromo\u20102'\u2010deoxyuridine (BrdU)<jats:sup>+<\/jats:sup> and Ki67<jats:sup>+<\/jats:sup> cells, while increased Doublecortin (DCX)\/BrdU double\u2010positive cells in SVZ. In cultured NSPCs, mGluR4 activation decreased the ratio of BrdU<jats:sup>+<\/jats:sup> cells, G2\/M\u2010phase cells, and inhibited Cyclin D1 expression, whereas it increased neuron\u2010specific class III \u03b2\u2010tubulin (Tuj1) expression and the number of Tuj1, DCX, and PSA\u2010NCAM\u2010positive 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\u2010regulated AKT phosphorylation and up\u2010regulated expression of the phosphatase and tensin homolog protein (PTEN) in NSPCs culture. Moreover VU0155041\u2010induced proliferating inhibition and neuronal differentiating amplification in NSPCs were significantly hampered by VO\u2010OHpic, a PTEN inhibitor. We conclude that activation of mGluR4 in SVZ\u2010derived NSPCs suppresses proliferation and enhances their neuronal differentiation, and regulation of PTEN may be involved as a potential intracellular target of mGluR4 signal.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14984-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:bold>Cover Image for this issue:<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.15052\">https:\/\/doi.org\/10.1111\/jnc.15052<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14984","type":"journal-article","created":{"date-parts":[[2020,2,13]],"date-time":"2020-02-13T05:01:57Z","timestamp":1581570117000},"page":"465-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["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"],"prefix":"10.1111","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-101X","authenticated-orcid":false,"given":"Zhichao","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Neurobiology, Xi\u2019an Jiaotong University Health Science Center Xi\u2019an Shaanxi 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