Ono M, Kikusui T, Sasaki N, Ichikawa M, Mori Y, Murakami-Murofushi K
Graduate School of Humanities and Sciences, Ochanomizu University, Bunkyo-ku, Tokyo, Japan.
Neuroscience. 2008 Oct 28;156(4):1103-10. doi: 10.1016/j.neuroscience.2008.07.078. Epub 2008 Aug 22.
Weaning is one of the most important events that occur during the early stages of life. For example, precocious weaning is known to increase anxiety-related behaviors in rodents. Here, we demonstrate that in addition to increasing anxiety, early-weaning manipulations alter the accumulation of galactosylceramide, a specific myelin constituent, and the axonal structure of myelinated fibers in the amygdala of male Balb/c mice. We found that early-weaned male mice entered the open arms of an elevated plus-maze less frequently than normally weaned mice at 3 and 5 weeks of age, which indicates persistently higher anxiety levels. However, early-weaned females exhibited fewer entries into the open arms only at 5 weeks of age. Lipid analysis of mice amygdalas showed the early accumulation of galactosylceramide in early-weaned male, but not female, mice at 5 weeks. The precocious accumulation of galactosylceramide was observed only in the amygdala; galactosylceramide accumulation was not observed in the prefrontal cortex or hippocampus of early-weaned male mice. Electron microscopy showed an increase in the number and a decrease in the diameter of myelinated axons in the anterior part of the basolateral amygdala in early-weaned male mice at 5 weeks. These results suggest that the higher anxiety levels observed in early-weaned male mice could be related to precocious myelin formation in the anterior part of the basolateral amygdala.
断奶是生命早期阶段发生的最重要事件之一。例如，已知过早断奶会增加啮齿动物的焦虑相关行为。在此，我们证明，除了增加焦虑外，早期断奶操作还会改变半乳糖神经酰胺（一种特定的髓鞘成分）的积累以及雄性Balb/c小鼠杏仁核中髓鞘纤维的轴突结构。我们发现，在3周和5周龄时，早期断奶的雄性小鼠进入高架十字迷宫开放臂的频率低于正常断奶的小鼠，这表明其焦虑水平持续较高。然而，早期断奶的雌性小鼠仅在5周龄时进入开放臂的次数较少。对小鼠杏仁核的脂质分析显示，在5周龄时，早期断奶的雄性而非雌性小鼠中半乳糖神经酰胺提前积累。仅在杏仁核中观察到半乳糖神经酰胺的过早积累；在早期断奶雄性小鼠的前额叶皮层或海马体中未观察到半乳糖神经酰胺的积累。电子显微镜显示，在5周龄时，早期断奶雄性小鼠基底外侧杏仁核前部有髓轴突数量增加而直径减小。这些结果表明，早期断奶雄性小鼠中观察到的较高焦虑水平可能与基底外侧杏仁核前部的髓鞘过早形成有关。
