The role of TREM1 in regulating microglial polarization in sevoflurane-induced perioperative neurocognitive disorders

TREM1 在七氟醚诱发的围手术期神经认知障碍中调节小胶质细胞极化的作用

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作者:Chunchun Tang, Xue Zheng, Yuanping Zhong, Dongqin Chen, Yuhang Zhu, Sihui Wang, Liulin Xiong, Zhaoqiong Zhu

Abstract

Microglia-mediated neuroinflammatory responses play a key role in perioperative neurocognitive disorders (PND). Triggering receptor expressed on myeloid cells-1 (TREM1) has been shown to be a key regulator of inflammation. However, its role in PND remains largely unknown. This study aimed to evaluate the role of TREM1 in sevoflurane-induced PND. We applied AAV knockdown TREM1 in hippocampal microglia in aging mice. The mice were then subjected to neurobehavioral and biochemical testing after the intervention of sevoflurane. We found that sevoflurane inhalation can cause PND in mice, increase hippocampal TREM1 expression, polarize microglia to M1 type, upregulate TNF-α and IL-1β expression (pro-inflammatory), and inhibit TGF-β and IL-10 expression (anti-inflammatory). Knocking down TREM1 can improve sevoflurane-induced cognitive dysfunction, reduce M1 type marker iNOS, and increase M2 type marker ARG, improving the neuroinflammation. TREM1 is a target for sevoflurane-induced PND prevention.

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