Machhor Nedal, Balaji Thankappa, Raju Tonse N K
Department of Pediatrics, Division of Neonatology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Life Sci. 2004 Feb 27;74(15):1925-35. doi: 10.1016/j.lfs.2003.09.044.
In this study, we investigated the effect of dexamethasone on the long-term learning and memory functions in developing rats. In Sprague-Dawley rat pups, we administered a daily dose of dexamethasone (0.5 mg/kg/day) for three consecutive days in three groups of animals: the "ultra-early" group received steroids on postnatal days (PND) 1-3; the "early" group received the drug on PNDs 8-10, and the "late" group received the drug on PNDs 28-30. The control group was not given any medication. All animals underwent structured CNS examinations beginning on PND 15, and continued through PND 20. The pups were tested for spatial learning and memory functions using the Morris Water Maze (MWM) on PNDs 31 through 35, 45 through 49, and 59 through 63. They were also tested for reward-based learning and memory functions using Radial Arm Maze (RAM) on PNDs 70 through 72. We analyzed the effect of dexamethasone, postnatal age, and sex on neurological milestones, and learning and memory functions. We found that neurological examination findings were similar in all groups, as were the results of the reward-based learning using RAM. However, in the MWM, the total distance of swimming and the total time to find the hidden platform showed considerable difference among the groups. Although these functions improved with postnatal age, the female pups in all three steroid groups, and the male pups in the late-steroid group lagged significantly in learning and memory functions compared to the controls, and such lags were transient. However, the interaction terms between dexamethasone, age, and sex were also significant in MWM test results. Steroids administered postnatally may have transient, retarding effect on learning and memory functions, and that animal age and sex may modify such effects. Such lags are not global, but specific to the types of memory tests used, implicating different neural circuitries in the pathogenesis of such abnormalities. Although transient, if such adverse effects occur at critical phases during brain maturation, the implications for poor, long-term outcomes may be more significant. The mechanisms underlying such changes need to be explored.
在本研究中，我们调查了地塞米松对发育中大鼠长期学习和记忆功能的影响。在斯普拉格-道利大鼠幼崽中，我们在三组动物中连续三天每日给予地塞米松剂量（0.5毫克/千克/天）：“超早期”组在出生后第1至3天接受类固醇；“早期”组在出生后第8至10天接受药物，“晚期”组在出生后第28至30天接受药物。对照组未给予任何药物。所有动物从出生后第15天开始接受结构化中枢神经系统检查，并持续至出生后第20天。幼崽在出生后第31至35天、45至49天以及59至63天使用莫里斯水迷宫（MWM）测试空间学习和记忆功能。它们还在出生后第70至72天使用放射状臂迷宫（RAM）测试基于奖励的学习和记忆功能。我们分析了地塞米松、出生后年龄和性别对神经发育里程碑以及学习和记忆功能的影响。我们发现所有组的神经检查结果相似，使用RAM进行的基于奖励的学习结果也相似。然而，在MWM中，游泳总距离和找到隐藏平台的总时间在各组之间存在显著差异。尽管这些功能随着出生后年龄的增长而改善，但所有三个类固醇组中的雌性幼崽以及晚期类固醇组中的雄性幼崽在学习和记忆功能方面与对照组相比明显滞后，并且这种滞后是短暂的。然而在地塞米松、年龄和性别之间的交互项在MWM测试结果中也很显著。出生后给予的类固醇可能对学习和记忆功能有短暂的延缓作用，并且动物年龄和性别可能会改变这种作用。这种滞后并非全局性的，而是特定于所使用的记忆测试类型，这表明不同的神经回路参与了此类异常的发病机制。尽管是短暂的，但如果这种不良影响发生在大脑成熟的关键阶段，对长期不良后果的影响可能会更显著。需要探索这种变化背后的机制。
