• Xinghua Ren, Siyi Zhang, Yongyan Yang, Annie Song, Feng Liang, Yiying Zhang, Yuanlin Dong, Xu Wu, and Zhongcong Xie.
• From the Department of Forensic Pathology' School of Forensic Medicine, China Medical University, Shenyang North New Area, Shenyang, Liaoning, China.
• Anesth. Analg. 2023 Apr 1; 136 (4): 779788779-788.

BackgroundKetamine is an intravenous anesthetic. However, whether ketamine can induce neurotoxicity and neurobehavioral deficits remains largely unknown. Delirium is a syndrome of acute brain dysfunction associated with anesthesia and surgery in patients, and tau protein may contribute to postoperative delirium. Finally, ketamine may affect the function of the endosome, the key organelle for tau release from neurons. Therefore, we set out to determine the effects of ketamine on delirium-like behavior in mice and on tau trafficking in cultured cells.MethodsWe used the buried-food test, open-field test, and Y-maze test in adult mice to assess the presence of delirium-like behavior in mice. We quantified tau amounts in the serum of mice. We used cell fraction methods to determine the effects of ketamine on tau intracellular trafficking, extracellular release, and endosome trafficking in cultured cells.ResultsKetamine induced delirium-like behavior in mice and increased tau amounts in serum of mice. The ketamine treatments also led to increased accumulation of endosomes, as evidenced by increased endosomal markers Rab5 and Rab7. Moreover, ketamine inhibited endosome maturation, demonstrated by decreased membrane-bound but increased cytoplasm amounts of Rab5 and Rab7. Consequently, ketamine increased tau in the endosomes of cultured cells and the cell culture medium.ConclusionsThese data suggest that ketamine may interfere with intracellular tau trafficking and induce delirium-like behavior, promoting future research regarding the potential neurotoxicity of anesthetics.Copyright © 2020 International Anesthesia Research Society.

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