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GPR17 mediates ischemia-like neuronal injury via microglial activation

  • Authors:
    • Bing Zhao
    • Hao Wang
    • Cai‑Xia Li
    • Sheng‑Wen Song
    • San‑Hua Fang
    • Er‑Qing Wei
    • Qiao‑Juan Shi
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China, Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China, Experimental Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2750-2762
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    Published online on: August 29, 2018
       https://doi.org/10.3892/ijmm.2018.3848
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Abstract

GPR17 is a G (i)-coupled dual receptor, linked to P2Y and CysLT receptors stimulated by uracil nucleotides and cysteinyl leukotrienes, respectively. Recent evidence has demonstrated that GPR17 inhibition ameliorates the progression of cerebral ischemic injury by regulating neuronal death and microglial activation. The present study aimed to assess the detailed regulatory roles of this receptor in oxygen‑glucose deprivation/recovery (OGD/R)‑induced ischemia‑like injury in vitro and explore the underlying mechanism. The results demonstrated that OGD/R induced ischemic neuronal injury and microglial activation, including enhanced phagocytosis and increased inflammatory cytokine release in neuron‑glial mixed cultures of cortical cells. GPR17 upregulation during OGD/R was spatially and temporally correlated with neuronal injury and microglial activation. In addition, GPR17 knockdown inhibited OGD/R‑induced responses in neuron‑glial mixed cultures. GPR17 knockdown also attenuated cell injury induced by the agonist leukotriene D4 (LTD4) or uridine 5'‑diphosphate (UDP) in neuron‑glial mixed cultures. However, GPR17 knockdown did not affect OGD/R‑induced ischemic neuronal injury in primary cultures of neurons. In primary astrocyte cultures, neither GPR17 nor OGD/R induced injury. By contrast, GPR17 knockdown ameliorated OGD/R‑induced microglial activation, boosting phagocytosis and inflammatory cytokine release in primary microglia cultures. Finally, the results demonstrated that the conditioned medium of microglia pretreated with OGD/R induced neuronal death, and the neuronal injury was significantly inhibited by GPR17 knockdown. These findings suggested that GPR17 may mediate ischemia‑like neuronal injury and microglial activation in vitro; however, the protective effects on ischemic neuronal injury might depend upon microglial activation. Whether GPR17 regulates neuronal injury mediated by oligodendrocyte linkage remains to be investigated.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao B, Wang H, Li CX, Song SW, Fang SH, Wei EQ and Shi QJ: GPR17 mediates ischemia-like neuronal injury via microglial activation. Int J Mol Med 42: 2750-2762, 2018.
APA
Zhao, B., Wang, H., Li, C., Song, S., Fang, S., Wei, E., & Shi, Q. (2018). GPR17 mediates ischemia-like neuronal injury via microglial activation. International Journal of Molecular Medicine, 42, 2750-2762. https://doi.org/10.3892/ijmm.2018.3848
MLA
Zhao, B., Wang, H., Li, C., Song, S., Fang, S., Wei, E., Shi, Q."GPR17 mediates ischemia-like neuronal injury via microglial activation". International Journal of Molecular Medicine 42.5 (2018): 2750-2762.
Chicago
Zhao, B., Wang, H., Li, C., Song, S., Fang, S., Wei, E., Shi, Q."GPR17 mediates ischemia-like neuronal injury via microglial activation". International Journal of Molecular Medicine 42, no. 5 (2018): 2750-2762. https://doi.org/10.3892/ijmm.2018.3848
Copy and paste a formatted citation
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Spandidos Publications style
Zhao B, Wang H, Li CX, Song SW, Fang SH, Wei EQ and Shi QJ: GPR17 mediates ischemia-like neuronal injury via microglial activation. Int J Mol Med 42: 2750-2762, 2018.
APA
Zhao, B., Wang, H., Li, C., Song, S., Fang, S., Wei, E., & Shi, Q. (2018). GPR17 mediates ischemia-like neuronal injury via microglial activation. International Journal of Molecular Medicine, 42, 2750-2762. https://doi.org/10.3892/ijmm.2018.3848
MLA
Zhao, B., Wang, H., Li, C., Song, S., Fang, S., Wei, E., Shi, Q."GPR17 mediates ischemia-like neuronal injury via microglial activation". International Journal of Molecular Medicine 42.5 (2018): 2750-2762.
Chicago
Zhao, B., Wang, H., Li, C., Song, S., Fang, S., Wei, E., Shi, Q."GPR17 mediates ischemia-like neuronal injury via microglial activation". International Journal of Molecular Medicine 42, no. 5 (2018): 2750-2762. https://doi.org/10.3892/ijmm.2018.3848
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