Details

Autor(en) / Beteiligte

• Zhang, Zhichao
• Zheng, Xiaoyan
• Liu, Yingfei
• Luan, Yan
• Wang, Li
• Zhao, Lingyu
• Zhang, Jianshui
• Tian, Yumei
• Lu, Haixia
• Chen, Xinlin
• Liu, Yong

Titel

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

Ist Teil von

• Journal of neurochemistry, 2021-02, Vol.156 (4), p.465-480

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2021

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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. Neural stem/progenitor cells (NSPCs) persist in the brain throughout life, providing novel therapeutic strategies in repairing nervous injury. In this study, we show that mGluR4 activation could inhibit the NSPCs proliferation and promote neuronal differentiation, and PTEN acts as an intracellular target of mGluR4 in NSPCs. These results may reveal the tremendous possibility of mGluR4 as a drug target in neural regenerative therapy of central nervous system damage. Cover Image for this issue: https://doi.org/10.1111/jnc.15052.