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
Autor: | Xinlin Chen, Yan Luan, Yu-mei Tian, Y. Liu, Li Wang, Zhichao Zhang, Haixia Lu, Yong Liu, Xiaoyan Zheng, Lingyu Zhao, Jianshui Zhang |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Doublecortin Protein Cyclohexanecarboxylic Acids Neurogenesis Gene Expression Subventricular zone Receptors Metabotropic Glutamate Biochemistry Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Neural Stem Cells Lateral Ventricles medicine Animals Tensin PTEN Anilides Cyclic adenosine monophosphate Progenitor cell Cells Cultured Cell Proliferation Dose-Response Relationship Drug biology Chemistry Metabotropic glutamate receptor 4 PTEN Phosphohydrolase Cell Differentiation Rats Cell biology Doublecortin 030104 developmental biology medicine.anatomical_structure biology.protein 030217 neurology & neurosurgery |
Zdroj: | Journal of Neurochemistry. 156:465-480 |
ISSN: | 1471-4159 0022-3042 |
Popis: | 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. Cover Image for this issue: https://doi.org/10.1111/jnc.15052. |
Databáze: | OpenAIRE |
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