Ketamine is a recreational drug that causes emotional and cognitive impairments, but its specific mechanisms of action are still unclear. Recent evidence suggests that Tau protein phosphorylation and targeted delivery to the postsynaptic area are closely related to its neurotoxicity, and our recent studies have shown that long-term ketamine administration causes excessive Tau protein phosphorylation. However, the regulatory mechanism of Tau protein phosphorylation induced by ketamine has not been clarified. In the present study, we administered a single ketamine injection and long-term (6 months) ketamine injections in C57BL/6 mice, to investigate the effects of different doses of ketamine on the expression levels of Tau protein and its phosphorylation, the expression levels and activities of the related protein phosphokinases GSK-3β and CDK5, and the expression levels and activities of the related protein phosphatases PP2A and PP2B in the mouse hippocampus. Our results showed that both single-dose and long-term ketamine administration induced excessive phosphorylation of the Tau protein at ser202/thr205 and ser396. A single ketamine administration caused an increase in the activity of GSK-3β (at high doses) and a decrease in the activity of PP2A. On the other hand, long-term ketamine administration resulted in an increase in the activities of GSK-3β (at high doses) and CDK5, and a decrease in the activity of PP2A. Our results indicate that GSK-3β, CDK5, and PP2A may be involved in ketamine-induced Tau protein phosphorylation.

氯胺酮是一种会导致情绪和认知障碍的消遣性药物，但其具体作用机制尚不清楚。最近的证据表明，Tau 蛋白磷酸化和靶向传递到突触后区域与其神经毒性密切相关，我们最近的研究表明，长期服用氯胺酮会导致 Tau 蛋白过度磷酸化。然而，氯胺酮诱导Tau蛋白磷酸化的调控机制尚未阐明。在本研究中，我们对 C57BL/6 小鼠进行单次氯胺酮注射和长期（6 个月）氯胺酮注射，以研究不同剂量氯胺酮对 Tau 蛋白表达水平及其磷酸化、表达水平的影响。相关蛋白磷酸激酶 GSK-3β 和 CDK5 的活性和活性，以及相关蛋白磷酸酶PP2A和PP2B在小鼠海马中的表达水平和活性。我们的结果表明，单剂量和长期氯胺酮给药均会诱导 Tau 蛋白在 ser202/thr205 和 ser396 处过度磷酸化。单次氯胺酮给药导致 GSK-3β（高剂量）活性增加和 PP2A 活性降低。另一方面，长期服用氯胺酮导致 GSK-3β（高剂量）和 CDK5 活性增加，PP2A 活性降低。我们的结果表明 GSK-3β、CDK5 和 PP2A 可能参与氯胺酮诱导的 Tau 蛋白磷酸化。我们的结果表明，单剂量和长期氯胺酮给药均会诱导 Tau 蛋白在 ser202/thr205 和 ser396 处过度磷酸化。单次氯胺酮给药导致 GSK-3β（高剂量）活性增加和 PP2A 活性降低。另一方面，长期服用氯胺酮导致 GSK-3β（高剂量）和 CDK5 活性增加，PP2A 活性降低。我们的结果表明 GSK-3β、CDK5 和 PP2A 可能参与氯胺酮诱导的 Tau 蛋白磷酸化。我们的结果表明，单剂量和长期氯胺酮给药均会诱导 Tau 蛋白在 ser202/thr205 和 ser396 处过度磷酸化。单次氯胺酮给药导致 GSK-3β（高剂量）活性增加和 PP2A 活性降低。另一方面，长期服用氯胺酮导致 GSK-3β（高剂量）和 CDK5 活性增加，PP2A 活性降低。我们的结果表明 GSK-3β、CDK5 和 PP2A 可能参与氯胺酮诱导的 Tau 蛋白磷酸化。长期服用氯胺酮导致 GSK-3β（高剂量）和 CDK5 活性增加，PP2A 活性降低。我们的结果表明 GSK-3β、CDK5 和 PP2A 可能参与氯胺酮诱导的 Tau 蛋白磷酸化。长期服用氯胺酮导致 GSK-3β（高剂量）和 CDK5 活性增加，PP2A 活性降低。我们的结果表明 GSK-3β、CDK5 和 PP2A 可能参与氯胺酮诱导的 Tau 蛋白磷酸化。