最近的研究發(fā)現(xiàn),，全麻藥物對發(fā)展中的神經(jīng)元具有神經(jīng)毒性，引起學(xué)習(xí)和記憶能力障礙及行為異常,。氯胺酮是小兒常用全麻藥物,，臨床回顧性研究發(fā)現(xiàn)3歲之前小兒接受過較長時間的手術(shù)，或因手術(shù)需要曾多次用過氯胺酮,，在學(xué)齡期表現(xiàn)為學(xué)習(xí)與記憶能力障礙及行為異常,，課題組推測這些異常表現(xiàn)可能與氯胺酮的潛在神經(jīng)毒性有關(guān)?！吨袊窠?jīng)再生研究（英文版）》雜志2013年6月17期出版的一項關(guān)于“Ketamine induces tau hyperphosphorylation at serine 404 in the hippocampus of neonatal rats”的研究,，應(yīng)用分子生物學(xué)技術(shù)從基因、蛋白質(zhì)水平觀察到,，常用全麻藥物氯胺酮可誘導(dǎo)發(fā)展中神經(jīng)元呈現(xiàn)tau蛋白磷酸化及神經(jīng)元毒性,。結(jié)果證明，氯胺酮可導(dǎo)致新生大鼠海馬神經(jīng)元微管排列紊亂,，可使新生鼠海馬異常磷酸化tau蛋白mRNA的表達提高,，誘導(dǎo)新生大鼠海馬Tau蛋白過度磷酸化位點在S404而不在S396,。作者認為，氯胺酮可能通過tau蛋白Ser404位點過度磷酸化,，以及tau蛋白過度磷酸化導(dǎo)致微管結(jié)構(gòu)破壞和損傷軸突運輸,，最終導(dǎo)致神經(jīng)細胞死亡而產(chǎn)生對新生小鼠的神經(jīng)毒性。實驗結(jié)果提示,，目前廣泛使用的兒科全麻藥氯胺酮可能是影響兒童學(xué)習(xí)能力的一個危險因素,。（生物谷 Bioon.com）
電鏡下(× 3 500)見給予胺碘酮的新生鼠海馬組織微管排列紊亂
生物谷推薦的英文摘要
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.
