Ahmadian-Attari Mohammad Mahdi, Dargahi Leila, Mosaddegh Mahmoud, Kamalinejad Mohammad, Khallaghi Behzad, Noorbala Fatemeh, Ahmadiani Abolhassan
Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurotox Res. 2015 Aug;28(2):95-107. doi: 10.1007/s12640-015-9525-0. Epub 2015 Mar 18.
Alzheimer's disease (AD) is a primary neurodegenerative disorder associated with progressive memory impairment. Recent studies suggest that hypothermia may contribute to the development and exacerbation of AD. The aim of this study was to investigate the role of chronic hypothermia on spatial learning and memory performance as well as brain immunohistochemical (IHC) and molecular changes. Four groups of male rats were placed in cold water (3.5 ± 0.5 °C) once a day for 1, 3, 6, and 14 days, four other groups were placed in warm water (32 °C) as the control groups to eliminate the effect of swimming stress, and one more group which comprised intact animals that were kept in a normothermic situation and had no swimming stress. Twenty-four hours after the last intervention, spatial learning and memory were assessed, using the modified Morris water maze. After the behavioral test, the rats' brains were removed for IHC and Western blotting. The results showed that memory retrieval is impaired after 14 days of cold water-induced hypothermia (CWH) (P < 0.05). IHC showed the formation of beta-amyloid plaques after a 14-day CWH. The molecular changes demonstrated that a 14-day CWH induces tau hyperphosphorylation, apoptosis, and reduces COX-II expression. Therefore, chronic CWH, independent of forced swimming stress, impairs learning and memory through molecular mechanisms similar to those of AD. In conclusion, CWH may serve as an important model to assess the role of hypothermia in AD pathogenesis.
阿尔茨海默病（AD）是一种与进行性记忆障碍相关的原发性神经退行性疾病。最近的研究表明，体温过低可能会导致AD的发生和加重。本研究的目的是探讨慢性体温过低对空间学习和记忆能力以及脑免疫组织化学（IHC）和分子变化的作用。将四组雄性大鼠每天置于冷水（3.5±0.5°C）中1、3、6和14天，另外四组置于温水（32°C）中作为对照组，以消除游泳应激的影响，还有一组为完整动物，置于常温环境中，无游泳应激。在最后一次干预24小时后，使用改良的莫里斯水迷宫评估空间学习和记忆能力。行为测试后，取出大鼠大脑进行免疫组织化学和蛋白质印迹分析。结果显示，冷水诱导体温过低（CWH）14天后记忆恢复受损（P<0.05）。免疫组织化学显示，CWH 14天后出现β-淀粉样蛋白斑块形成。分子变化表明，CWH 14天可诱导tau蛋白过度磷酸化、细胞凋亡，并降低COX-II表达。因此，独立于强迫游泳应激的慢性CWH通过与AD相似的分子机制损害学习和记忆。总之，CWH可能是评估体温过低在AD发病机制中作用的重要模型。
