Win-Shwe Tin-Tin, Kageyama Shiho, Tsukahara Shinji, Nakajima Daisuke, Fujimaki Hidekazu
Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
J UOEH. 2010 Jun 1;32(2):127-40. doi: 10.7888/juoeh.32.127.
D-cycloserine (DCS), a partial N-methyl-D-aspartate (NMDA) receptor agonist, is a well-known cognitive enhancer. To investigate the effect of DCS in cognitive function following toluene exposure, eight-week-old male C3H/HeN mice were exposed to filtered air (0 ppm) or 50 ppm toluene for 6 h a day on 5 consecutive days a week for 6 weeks. The day after the day of final exposure, a spatial learning task was performed using a Morris water maze apparatus. During the learning task, some mice were treated with DCS intraperitoneally (20 mg/kg) 30 min before the first trial of the acquisition phase and probe trial. After completion of the spatial learning task, the hippocampus was collected from each mouse to examine memory function-related gene expression using the real-time RT-PCR method. During the acquisition phase, on day 3 and 4, toluene-exposed mice with DCS treatment showed significantly better learning performance than corresponding saline treated groups. Moreover, the toluene-exposed mice with DCS treatment also showed significantly improved memory retention during the probe trial and up-regulation of hippocampal NMDA receptor subunit 2B mRNA expression compared with the saline treated groups. Our findings indicate that a subunit-specific modulation of hippocampal NMDA receptor mRNA expression by DCS contributes to improvement of spatial learning performance in mice following toluene exposure.
D-环丝氨酸（DCS）是一种部分N-甲基-D-天冬氨酸（NMDA）受体激动剂，是一种著名的认知增强剂。为了研究DCS在甲苯暴露后对认知功能的影响，将8周龄雄性C3H/HeN小鼠每天暴露于过滤空气（0 ppm）或50 ppm甲苯中，每周连续5天，每天6小时，共6周。在最后一次暴露后的第二天，使用莫里斯水迷宫装置进行空间学习任务。在学习任务期间，一些小鼠在习得阶段的第一次试验和探索试验前30分钟腹腔注射DCS（20 mg/kg）。完成空间学习任务后，从每只小鼠身上采集海马体，使用实时RT-PCR方法检测与记忆功能相关的基因表达。在习得阶段的第3天和第4天，接受DCS治疗的甲苯暴露小鼠的学习表现明显优于相应的生理盐水治疗组。此外，与生理盐水治疗组相比，接受DCS治疗的甲苯暴露小鼠在探索试验中的记忆保持能力也显著提高，海马体NMDA受体亚基2B mRNA表达上调。我们的研究结果表明，DCS对海马体NMDA受体mRNA表达的亚基特异性调节有助于改善甲苯暴露后小鼠的空间学习表现。
