Franco-Pons Neus, Torrente Margarita, Colomina Maria Teresa, Vilella Elisabet
Unitat de Psiquiatria i Psicologia Mèdica, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, C/Sant Llorenç 21, 43201 Reus, Spain.
Toxicol Lett. 2007 Mar 30;169(3):205-13. doi: 10.1016/j.toxlet.2007.01.010. Epub 2007 Feb 2.
The neurotoxicant cuprizone has been used extensively to create a mouse model of demyelination. However, the effects on behavior of cuprizone treatment have not been previously reported. We have analyzed the behavioral changes of mice given a diet containing 0.2% cuprizone for 6 weeks followed by 6 weeks of recovery. Behavior was assessed using a range of tests: the functional observation battery, the open-field test and the rota-rod test. Concurrent with the start of demyelination, at 3 and 4 weeks of 0.2% cuprizone treatment, the animals exhibited an increase in central nervous system activity and an inhibited anxiogenic response to the novelty challenge test. At 5 weeks of treatment (the period of maximal demyelination) equilibrium was altered and sensorimotor reactivity was also affected. Further, rota-rod analysis demonstrated that the treated group had poorer motor co-ordination than control animals. This effect was not reversed 6 weeks after cuprizone withdrawal. The animals in the recovery period also exhibited difficulties in the rota-rod progressive learning task. Our results indicate that behavioral deficits follow the course of demyelination-remyelination induced by administration of 0.2% cuprizone, and that some of the changes persist even after 6 weeks on normal diet.
神经毒剂铜螯合剂已被广泛用于建立脱髓鞘小鼠模型。然而，此前尚未报道过铜螯合剂治疗对行为的影响。我们分析了给予含0.2%铜螯合剂饮食6周后再恢复6周的小鼠的行为变化。使用一系列测试评估行为：功能观察组合、旷场试验和转棒试验。在脱髓鞘开始时，即在0.2%铜螯合剂治疗的第3周和第4周，动物表现出中枢神经系统活动增加，对新异刺激挑战试验的焦虑反应受到抑制。在治疗第5周（最大脱髓鞘期），平衡发生改变，感觉运动反应性也受到影响。此外，转棒分析表明，治疗组的运动协调性比对照动物差。在停用铜螯合剂6周后，这种效应并未逆转。恢复期的动物在转棒渐进学习任务中也表现出困难。我们的结果表明，行为缺陷与给予0.2%铜螯合剂诱导的脱髓鞘-再髓鞘形成过程一致，并且即使在正常饮食6周后，一些变化仍然存在。
