Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke

Abstract 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 wheth...

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Autores principales:	Ping Li, Tingting Shen, Xue Luo, Ju Yang, Zhen Luo, Yulong Tan, Genlin He, Zeze Wang, Xueting Yu, Ying Wang, Xuesen Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ffffee16cf03490599b2fb08328301bf
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spelling	oai:doaj.org-article:ffffee16cf03490599b2fb08328301bf2021-12-02T16:07:03ZModulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke10.1038/s41598-021-92906-52045-2322https://doaj.org/article/ffffee16cf03490599b2fb08328301bf2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92906-5https://doaj.org/toc/2045-2322Abstract 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.Ping LiTingting ShenXue LuoJu YangZhen LuoYulong TanGenlin HeZeze WangXueting YuYing WangXuesen YangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ping Li Tingting Shen Xue Luo Ju Yang Zhen Luo Yulong Tan Genlin He Zeze Wang Xueting Yu Ying Wang Xuesen Yang Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
description	Abstract 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.
format	article
author	Ping Li Tingting Shen Xue Luo Ju Yang Zhen Luo Yulong Tan Genlin He Zeze Wang Xueting Yu Ying Wang Xuesen Yang
author_facet	Ping Li Tingting Shen Xue Luo Ju Yang Zhen Luo Yulong Tan Genlin He Zeze Wang Xueting Yu Ying Wang Xuesen Yang
author_sort	Ping Li
title	Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
title_short	Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
title_full	Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
title_fullStr	Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
title_full_unstemmed	Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
title_sort	modulation of microglial phenotypes by dexmedetomidine through trem2 reduces neuroinflammation in heatstroke
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ffffee16cf03490599b2fb08328301bf
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Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke

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