Onishchenko Natalia, Tamm Christoffer, Vahter Marie, Hökfelt Tomas, Johnson Jeffrey A, Johnson Delinda A, Ceccatelli Sandra
Division of Toxicology and Neurotoxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Toxicol Sci. 2007 Jun;97(2):428-37. doi: 10.1093/toxsci/kfl199. Epub 2007 Jan 4.
To investigate the long-term effects of developmental exposure to methylmercury (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water from gestational day 7 until day 7 after delivery. The behavior of offspring was monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage) designed for continuous long-term recording of the home cage behavior in social groups and complex analysis of basic activities and learning. In addition, spontaneous locomotion, motor coordination on the accelerating rotarod, spatial learning in Morris water maze, and depression-like behavior in forced swimming test were also studied. The analysis of behavior performed in the IntelliCage without social deprivation occurred to be more sensitive in detecting alterations in activity and learning paradigms. We found normal motor function but decreased exploratory activity in MeHg-exposed male mice, especially at young age. Learning disturbances observed in MeHg-exposed male animals suggest reference memory impairment. Interestingly, the forced swimming test revealed a predisposition to depressive-like behavior in the MeHg-exposed male offspring. This study provides novel evidence that the developmental exposure to MeHg can affect not only cognitive functions but also motivation-driven behaviors.
为了研究发育过程中暴露于甲基汞(MeHg)的长期影响,怀孕小鼠从妊娠第7天开始直至分娩后第7天,通过饮用水以0.5毫克甲基汞/千克/天的剂量进行暴露。使用自动系统(IntelliCage)在5 - 15周龄和26 - 36周龄时监测后代的行为,该系统设计用于连续长期记录社会群体中笼内行为,并对基本活动和学习进行复杂分析。此外,还研究了自发运动、在加速转棒上的运动协调性、在莫里斯水迷宫中的空间学习以及强迫游泳试验中的抑郁样行为。在没有社会剥夺的情况下,对IntelliCage中进行的行为分析在检测活动和学习模式的改变方面更为敏感。我们发现甲基汞暴露的雄性小鼠运动功能正常,但探索活动减少,尤其是在幼年时。在甲基汞暴露的雄性动物中观察到的学习障碍表明参考记忆受损。有趣的是,强迫游泳试验显示甲基汞暴露的雄性后代有抑郁样行为倾向。这项研究提供了新的证据,表明发育过程中暴露于甲基汞不仅会影响认知功能,还会影响动机驱动的行为。