Nitrous oxide decreases cortical methionine synthase transiently but produces lasting memory impairment in aged rats
Nitrous oxide decreases cortical methionine synthase transiently but produces lasting memory impairment in aged rats
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DOI：
10.1213/01.ane.0000266491.53318.20
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发表时间：
2007-07-01
影响因子：
5.7
通讯作者：
Crosby, Gregory
中科院分区：
文献类型：
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作者：
Culley, Deborah J.;Raghavan, Sumati V.;Crosby, Gregory
背景技术背景：一氧化二氮是一种常用的麻醉剂，可抑制甲硫氨酸合酶的活性，甲硫氨酸合酶是一种参与甲基化反应和DNA合成与修复的酶。这种抑制触发了发育和成熟大脑中对空间记忆很重要的区域的空泡形成和神经元变性，提高了一氧化二氮可能对学习产生持续影响的可能性。为了测试这种可能性，我们将18个月大的Fischer 344大鼠随机分组，（每组n = 13）至70%一氧化二氮+30%氧气或70%氮气+30%氧气（对照）的4小时，并使用12-在吸入一氧化二氮后2天开始进行14天的臂放射状迷宫。在单独的，相同的治疗组的大鼠，我们测量了蛋氨酸合成酶的活性在皮质和肝脏在一氧化二氮暴露结束后，2天后（n = 3大鼠每组每个时间点）使用一个标准的assay.Results：肝脏和皮质蛋氨酸合成酶被抑制在一氧化二氮吸入（6%和23%的控制，分别在肝脏和皮质，P < 0.01）。肝酶活性持续低迷2天后，而皮质酶活性恢复。对照组和一氧化二氮处理组大鼠的错误率无差异。结论：70%氧化亚氮镇静可显著降低老年大鼠皮层蛋氨酸合成酶活性，但对空间工作记忆有持续损害作用。
BACKGROUND: Nitrous oxide is a commonly used anesthetic that inhibits the activity of methionine synthase, an enzyme involved in methylation reactions and DNA synthesis and repair. This inhibition triggers vacuole formation and degeneration of neurons in areas of the developing and mature brain that are important for spatial memory, raising the possibility that nitrous oxide might have sustained effects on learning.METHODS: To test this possibility, we randomized 18-month-old Fischer 344 rats (n = 13 per group) to 4 h of 70% nitrous oxide + 30% oxygen or 70% nitrogen + 30% oxygen (control) and assessed memory using a 12-arm radial maze for 14 days beginning 2 days after nitrous oxide inhalation. In separate, identically treated groups of rats, we measured methionine synthase activity in the cortex and liver at the end of nitrous oxide exposure and 2 days later (n = 3 rats per group per time point) using a standard assay.RESULTS: Liver and cortical methionine synthase was inhibited during nitrous oxide inhalation (6% and 23% of control in liver and cortex, respectively; P < 0.01). Liver enzyme activity remained depressed 2 days later, whereas cortical enzyme activity recovered. There was no difference in error rate between control and nitrous oxide treated rats. However, those exposed to nitrous oxide took more time to complete the maze and made fewer correct choices before first error (P < 0.05).CONCLUSIONS: Sedation with 70% nitrous oxide profoundly, but transiently, reduces the activity of cortical methionine synthase but produces lasting impairment in spatial working memory in aged rats.