title: Dexmedetomidine Regulates 6-hydroxydopamine-Induced Microglial Polarization.
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.
authors.affiliation: 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.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Xuechang
authors.initials: X
authors.lastname: Han
authors.affiliation: 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. qzxing0506@163.com.
authors.forename: Qunzhi
authors.initials: Q
authors.lastname: Xing
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018836:Inflammation Mediators; D020927:Dexmedetomidine; D016627:Oxidopamine
keywords: 6-Hydroxydopamine (6-OHDA); Arginase-1 (Arg-1); Dexmedetomidine; Microglia M2 polarization; STAT6