Wang Ji, Zhou Min, Wang Xiaobin, Yang Xiaoling, Wang Maohua, Zhang Chunxiang, Zhou Shuzhi, Tang Ni
Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
Department of Pharmacology, Rush Medical College, Rush University, Chicago, Illinois, United Stated of America.
PLoS One. 2014 Jun 10;9(6):e99855. doi: 10.1371/journal.pone.0099855. eCollection 2014.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic and anti-depressive drug. Recent studies suggest that ketamine enhances neuronal apoptosis in developing rats. The goal of this study is to explore whether ketamine could result in learning and memory impairment and neurodegeneration in adolescent rats, and if so, whether the effects of ketamine are associated with miR-214 and PTEN expression. Fifty-day-old SD rats were randomly divided into three groups receiving ketamine at 30, or 80 mg/kg, i.p. or saline for seven consecutive days. Twenty-four hours after the last treatment, learning and memory function were tested by the Morris water maze. The rats were then decapitated, and the brains were isolated for detection of neuronal apoptosis and protein PTEN expression by TUNEL and immunohistochemistry respectively. Expression levels of the miR-214 and PTEN in the hippocampus were measured by qRT-PCR and western blot analysis respectively. Ketamine administered to the adolescent rats at a dose of 80 mg/kg rather than the lower dose of 30 mg/kg caused learning and memory impairment, increased the number of apoptotic cells in the hippocampal CA1 region, cerebral cortex and subcortical region, decreased the miR-214 levels and increased PTEN protein expression in hippocampus. The results suggest that ketamine at a dose of 80 mg/kg in the adolescent rats is able to induce the learning and memory impairment and neurodegeneration, in which the down-regulation of miR-214 and high expression of PTEN protein may be involved.
氯胺酮是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，用作儿科全身麻醉药和抗抑郁药。最近的研究表明，氯胺酮可增强发育中大鼠的神经元凋亡。本研究的目的是探讨氯胺酮是否会导致青春期大鼠的学习记忆障碍和神经退行性变，如果是，氯胺酮的作用是否与miR-214和PTEN表达有关。将50日龄的SD大鼠随机分为三组，分别腹腔注射30或80mg/kg氯胺酮或生理盐水，连续7天。最后一次治疗后24小时，通过莫里斯水迷宫测试学习和记忆功能。然后将大鼠断头，分离大脑，分别通过TUNEL和免疫组织化学检测神经元凋亡和PTEN蛋白表达。分别通过qRT-PCR和蛋白质印迹分析测量海马中miR-214和PTEN的表达水平。以80mg/kg而非30mg/kg的剂量给青春期大鼠施用氯胺酮会导致学习和记忆障碍，增加海马CA1区、大脑皮层和皮层下区域的凋亡细胞数量，降低海马中miR-214水平并增加PTEN蛋白表达。结果表明，80mg/kg剂量的氯胺酮能够诱导青春期大鼠的学习记忆障碍和神经退行性变，其中可能涉及miR-214的下调和PTEN蛋白的高表达。
