Department of Psychiatry, Nara Medical University Faculty of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2009 Aug 31;33(6):978-85. doi: 10.1016/j.pnpbp.2009.05.006. Epub 2009 May 14.
Dysmyelination is hypothesized to be one of the causes of schizophrenic symptoms. Supporting this hypothesis, demyelination induced by cuprizone was recently shown to cause schizophrenia-like symptoms in adult rodents [Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, et al. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry 2008;13:697-708]. The present study asked if the timing of demyelination (i.e., juvenile period or adulthood) influenced abnormal behavior.
B57BL/6 mice were fed with 0.2% cuprizone either from postnatal day 29 (P29) to P56 (early demyelination group) or from P57 to P84 (late demyelination group), and then returned to normal mouse chow until P126, when the behavioral analysis was initiated.
In both groups, the intake of cuprizone for 28 days produced massive demyelination in the corpus callosum by the end of the treatment period, and subsequent normal feeding restored myelination by P126. In a Y-maze test, the spatial working memory was impaired in both groups right after the cuprizone feeding ceased, consistent with previous studies, whereas only the early demyelination group exhibited impaired working memory after remyelination took place. In an open field test, social interactions were decreased in the early demyelination group, but not in the late group. Novel cognition and anxiety-related behaviors were comparable between the two groups.
Our findings suggest that the timing of demyelination has substantial impacts on behaviors of adult mice.
脱髓鞘被认为是精神分裂症症状的原因之一。支持这一假说，最近研究发现，铜锌卟啉诱导的脱髓鞘可导致成年啮齿动物出现类似精神分裂症的症状[Xiao L, Xu H, Zhang Y, Wei Z, He J, Jiang W, et al. Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry 2008;13:697-708]。本研究旨在探讨脱髓鞘的时间（即幼年或成年）是否会影响异常行为。
B57BL/6 小鼠从出生后第 29 天（P29）至 P56 天（早期脱髓鞘组）或 P57 天至 P84 天（晚期脱髓鞘组）喂食 0.2%铜锌卟啉，然后恢复正常的鼠粮喂养至 P126 天，此时开始进行行为分析。
在两组中，28 天的铜锌卟啉喂养在治疗期末导致胼胝体大量脱髓鞘，随后的正常喂养在 P126 天恢复髓鞘。在 Y 迷宫测试中，两组在停止铜锌卟啉喂养后立即出现空间工作记忆受损，与之前的研究一致，而只有早期脱髓鞘组在髓鞘重新形成后出现工作记忆受损。在旷场测试中，早期脱髓鞘组的社交互动减少，但晚期脱髓鞘组没有减少。两组之间的新认知和焦虑相关行为没有差异。
我们的研究结果表明，脱髓鞘的时间对成年小鼠的行为有实质性的影响。
