Ketamine induces delirium-like behavior and interferes with endosomal tau trafficking
Xinghua Ren, Siyi Zhang, Yongyan Yang, Annie Song, Feng Liang, Yiying Zhang, Yuanlin Dong, Xu Wu, Zhongcong Xie
Summary
AI-generated from the abstractKetamine, an anesthetic and antidepressant, can induce delirium-like behavior in mice and increase tau protein in their blood. In cultured cells, ketamine disrupts endosome function—key organelles for tau release—by increasing endosomal markers Rab5 and Rab7, inhibiting endosome maturation, and boosting tau accumulation in endosomes and the culture medium. These findings suggest ketamine may interfere with tau trafficking, potentially contributing to neurotoxicity and delirium, warranting further research into anesthetic safety.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Adult mice and cultured cells |
| Intervention | Ketamine |
| Key finding | Ketamine induced delirium-like behavior and increased tau in mouse serum, and in cultured cells it disrupted endosome function and increased tau release. |
Abstract
Abstract Background Ketamine is an anesthetic and antidepressant drug. However, whether ketamine can induce neurotoxicity and neurobehavioral deficits remains largely unknown. Delirium is a syndrome of acute brain dysfunction that is very similar to the presentation after ketamine administration. The onset of postoperative delirium in patients is often accompanied by elevated tau in cerebrospinal fluid. And ketamine may affect 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. Methods We used the buried food test, open field test, and Y-maze test in adult mice to assess the occurrence of delirium-like behavior induced by ketamine. Quantified tau in the serum of mice with delirium-like behavior. And used cell fraction methods to determine the effects of ketamine on tau intracellular transfer, extracellular release and endosomes in cultured cells. Results Ketamine induced delirium-like behavior and increased tau in mouse serum. Ketamine treatment 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. Conclusion These data suggest that ketamine may interfere with intracellular tau trafficking and induce delirium-like behavior, promoting future research regarding neurotoxicity of anesthetics.