最近的研究发现，全麻药物对发展中的神经元具有神经毒性，引起学习和记忆能力障碍及行为异常。氯胺酮是小儿常用全麻药物，临床回顾性研究发现3岁之前小儿接受过较长时间的手术，或因手术需要曾多次用过氯胺酮，在学龄期表现为学习与记忆能力障碍及行为异常，课题组推测这些异常表现可能与氯胺酮的潜在神经毒性有关。《中国神经再生研究（英文版）》杂志2013年6月17期出版的一项关于“Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats”的研究，应用分子生物学技术从基因、蛋白质水平观察到，常用全麻药物氯胺酮可诱导发展中神经元呈现tau蛋白磷酸化及神经元毒性。结果证明，氯胺酮可导致新生大鼠海马神经元微管排列紊乱，可使新生鼠海马异常磷酸化tau蛋白mRNA的表达提高，诱导新生大鼠海马Tau蛋白过度磷酸化位点在S404而不在S396。作者认为，氯胺酮可能通过tau蛋白Ser404位点过度磷酸化，以及tau蛋白过度磷酸化导致微管结构破坏和损伤轴突运输，最终导致神经细胞死亡而产生对新生小鼠的神经毒性。实验结果提示，目前广泛使用的儿科全麻药氯胺酮可能是影响儿童学习能力的一个危险因素。（生物谷 Bioon.com）
电镜下(× 3 500)见给予胺碘酮的新生鼠海马组织微管排列紊乱
生物谷推荐的英文摘要
Neural Regeneration Research Doi:10.3969/j.issn.1673-5374.2013.17.007
Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats
Jin HY, Hu ZY, Dong MJ, Wu YD, Zhu ZR, Xu LL.
Male Wistar 7-day-old rats were injected with 40 mg/kg ketamine intraperitoneally, followed by threeadditional injections of 20 mg/kg ketamine each upon restoration of the righting reflex. Neonatal ratsinjected with equivalent volumes of saline served as controls. Hippocampal samples were collected at1, 7 or 14 days following administration. Electron microscopy showed that neuronal structure changednoticeably following ketamine treatment. Specifically, microtubular structure became irregular anddisorganized. Quantitative real time-PCR revealed that phosphorylated tau mRNA was upregulatedafter ketamine. Western blot analysis demonstrated that phosphorylated tau levels at serine 396initially decreased at 1 day after ketamine injection, and then gradually returned to control values. At14 days after injection, levels of phosphorylated tau were higher in the ketamine group than in thecontrol group. Tau protein phosphorylated at serine 404 significantly increased after ketamine injection,and then gradually decreased with time. However, the levels of tau protein at serine 404 weresignificantly greater in the ketamine group than in the control group until 14 days. The present resultsindicate that ketamine induces an increase of phosphorylated tau mRNA and excessivephosphorylation of tau protein at serine 404, causing disruption of microtubules in the neonatal rathippocampus and potentially resulting in damage to hippocampal neurons.
