Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke.
Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke.
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右美托咪定通过 TREM2 调节小胶质细胞表型可减少中暑时的神经炎症
DOI：
10.1038/s41598-021-92906-5
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发表时间：
2021-06-25
影响因子：
4.6
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Li P;Shen T;Luo X;Yang J;Luo Z;Tan Y;He G;Wang Z;Yu X;Wang Y;Yang X
目前尚无 FDA 批准的药物疗法可用于减少中暑后的神经炎症。先前的研究表明，右美托咪定（DEX）可以预防各种炎症相关疾病中的炎症和脑损伤。然而，没有人测试过 DEX 对中暑是否具有神经保护作用。在本研究中，我们重点关注小胶质细胞表型调节，以研究 DEX 体内和体外抗炎作用的机制。我们发现DEX治疗降低了小胶质细胞中CD68、iNOS、TNF-α和IL-1β的表达，并增加了CD206、Arg1、IL-10和TGF-β的表达，从而改善了中暑引起的小鼠神经炎症和脑损伤。 TREM2 的神经保护功能已通过阿尔茨海默氏病和 Nasu-Hakola 病的遗传学研究得到验证，DEX 在小胶质细胞中显着促进了 TREM2 的发挥。 TREM2 esiRNA 逆转了 DEX 诱导的 PI3K/Akt 信号传导激活。总体而言，这些研究结果表明，DEX 可能作为一种潜在的治疗方法，通过激活 PI3K/Akt 信号传导，通过 TREM2 改善中暑引起的神经炎症和脑损伤。
No FDA approved pharmacological therapy is available to reduce neuroinflammation following heatstroke. Previous studies have indicated that dexmedetomidine (DEX) could protect against inflammation and brain injury in various inflammation-associated diseases. However, no one has tested whether DEX has neuro-protective effects in heatstroke. In this study, we focused on microglial phenotypic modulation to investigate the mechanisms underlying the anti-inflammatory effects of DEX in vivo and in vitro. We found that DEX treatment reduced the expression of CD68, iNOS, TNF-α, and IL-1β, and increased the expression of CD206, Arg1, IL-10 and TGF-β in microglia, ameliorating heatstroke induced neuroinflammation and brain injury in mice. TREM2, whose neuro-protective function has been validated by genetic studies in Alzheimer’s disease and Nasu-Hakola disease, was significantly promoted by DEX in the microglia. TREM2 esiRNA reversed the DEX-induced activation of PI3K/Akt signalling. Overall these findings indicated that DEX may serve, as a potential therapeutic approach to ameliorate heatstroke induced neuroinflammation and brain injury via TREM2 by activating PI3K/Akt signalling.
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DOI：
10.1056/nejmoa1211851
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Guerreiro R;Wojtas A;Bras J;Carrasquillo M;Rogaeva E;Majounie E;Cruchaga C;Sassi C;Kauwe JS;Younkin S;Hazrati L;Collinge J;Pocock J;Lashley T;Williams J;Lambert JC;Amouyel P;Goate A;Rademakers R;Morgan K;Powell J;St George-Hyslop P;Singleton A;Hardy J;Alzheimer Genetic Analysis Group
通讯作者：
Alzheimer Genetic Analysis Group
MicroRNA-155 通过靶向小胶质细胞中的肝脏 X 受体 α 促进热应激诱发的炎症
影响因子：
5.3
作者：
Li, Ping;Wang, Gong;Yang, Xue-Sen
通讯作者：
Yang, Xue-Sen
影响因子：
15.1
作者：
Nance, Dwight M.;Sanders, Virginia M.
通讯作者：
Sanders, Virginia M.
影响因子：
6.1
作者：
Rizzi, M;Perego, C;Vezzani, A
通讯作者：
Vezzani, A
影响因子：
3.9
作者：
Stolzing, A;Wengner, A;Grune, T
通讯作者：
Grune, T