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Dexmedetomidine Regulates 6-hydroxydopamine-Induced Microglial Polarization

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Abstract

Microglia have undergone extensive characterization and have been shown to present distinct phenotypes, such as the M1 or M2 phenotypes, depending on their stimuli. As a highly specific neurotoxin, 6-hydroxydopamine (6-OHDA) can be used to further our understanding of the immune response in Parkinson’s disease (PD). Dexmedetomidine (DEX), a centrally selective α2-adrenoceptor agonist, performs very well as an anti-anxiety medication, sedative and analgesic. In the present study, we investigated the effects of DEX on 6-OHDA-induced microglial polarization. Our results indicate that treatment with 6-OHDA promotes microglial polarization toward the M1 state in BV2 microglia cells by increasing the release of interleukin (IL)-6, IL-1β, or tumor necrosis factor-α, which can be prevented by pretreatment with DEX. In addition, we found that 6-OHDA blocked IL-4-mediated microglial M2 polarization by suppressing expression of the microglial M2 markers arginase-1 (Arg-1), resistin-like α (Retnla/Fizz1), and chitinase 3-like 3 (Chi3l3/Ym1), which could be ameliorated by pretreatment with DEX. Notably, the inhibitory effects of 6-OHDA on IL-4-mediated induction of the anti-inflammatory marker genes IL-10, IL-13, and transforming growth factor-β2 could be significantly alleviated by pretreatment with DEX in a dose-dependent manner (P < 0.01). Mechanistically, alternations in the activation of signal transducer and activator of transcription 6 were involved in this process. These findings suggest that administration of DEX has the potential to interrupt the process of microgliosis in PD.

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, 24 Jinghua Road, Jianxi District, Luoyang, 471003, Henan, China

    Pei Zhang, Yu Li, Xuechang Han, Qunzhi Xing & Lei Zhao

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  1. Pei Zhang
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  2. Yu Li
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  3. Xuechang Han
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  4. Qunzhi Xing
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  5. Lei Zhao
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Correspondence to Qunzhi Xing.

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Zhang, P., Li, Y., Han, X. et al. Dexmedetomidine Regulates 6-hydroxydopamine-Induced Microglial Polarization. Neurochem Res 42, 1524–1532 (2017). https://doi.org/10.1007/s11064-017-2209-9

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  • DOI: https://doi.org/10.1007/s11064-017-2209-9

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