Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels
Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels
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DOI：
10.1111/j.1600-079x.2005.00302.x
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发表时间：
2006-04-01
影响因子：
10.3
通讯作者：
Machida, M
中科院分区：
文献类型：
--
作者：
Oyama, J;Murai, I;Machida, M
除了通过松果体切除术（PINX）在鸡中诱导脊柱侧凸之外，我们之前证明，去除松果体也会在双足大鼠中产生脊柱侧凸，这可以通过褪黑激素治疗来抑制。使用基因上循环褪黑激素水平较低的 C57BL/6J 小鼠，本研究的主要目的是研究 C57BL/6J 小鼠的双足行走是否对脊柱畸形具有与松果体切除的双足大鼠相同的影响。本研究分为两个阶段。第一个实验的目的是确定 C57BL/6J 小鼠品系在光:暗周期的光和暗阶段是否实际上表现出褪黑激素的血浆浓度和/或松果体含量降低。第二个实验的目的是评估； (i) C57BL/6J 小鼠中单独双足行走是否会诱发脊柱侧弯，以及 (ii) 另一种小鼠品系（即 C3H/HeJ）中双足行走的 PINX 是否具有与 C57BL/6J 小鼠中单独双足行走相似的效果，C3H/HeJ 通常表现出褪黑素合成和分泌的昼夜波动。作为对照的 C3H/HeJ 小鼠在黑暗阶段与亮阶段相比，褪黑激素的血浆浓度和松果体含量均显着增加。相比之下，C57BL/6J 小鼠的明期和暗期褪黑激素的循环水平或松果体含量没有差异。此外，两个阶段的血浆褪黑激素水平均低于检测限，松果体褪黑激素水平< C3H/HeJ 小鼠的 10%。 C57BL/6J 小鼠双足行走 40 周，诱发脊柱侧弯的概率为 64.3%，九只脊柱侧弯小鼠中的两只出现两个部位的脊柱畸形。 C3H/HeJ 小鼠的这种类型的行走导致脊柱侧弯的发生率较低（25%），并且受影响的动物只有一个脊柱侧弯部位。然而，PINX 与 C3H/HeJ 小鼠的双足行走相结合，产生的脊柱侧凸率 (70%) 与 C57BL/6J 小鼠相似，并且诱导了一些双重变形。这些结果证实了我们之前在大鼠中的观察结果，也支持了我们的假设，即褪黑激素以及双足行走似乎在实验哺乳动物脊柱侧弯中发挥着关键的致病作用。
In addition to the induction of scoliosis in chickens by pinealectomy (PINX), we previously demonstrated that removal of the pineal gland also produces scoliosis in bipedal rats, which can be inhibited by melatonin treatment. Using C57BL/6J mice with genetically low circulating melatonin levels, the main objective of the present study was to investigate whether bipedal ambulation in C57BL/6J mice has the same effects on spinal deformity as those seen in pinealectomized bipedal rats. The present study consisted of two phases. The aim of the first experiment was to determine whether the C57BL/6J mouse strain actually exhibits depressed plasma concentrations and/or pineal contents of melatonin during both the light and the dark phase of the light:dark cycle. The aims of the second experiment were to evaluate; (i) whether bipedal ambulation alone in the C57BL/6J mouse induces scoliosis, and (ii) whether PINX with bipedal ambulation in another mouse strain, i.e. C3H/HeJ, which normally exhibits diurnal fluctuations in melatonin synthesis and secretion, has effects similar to those of bipedal ambulation alone in C57BL/6J mice. C3H/HeJ mice, serving as controls, showed significant increases in both plasma concentrations and pineal contents of melatonin during the dark phase when compared with the light phase. In contrast, there were no differences in either circulating levels or pineal contents of melatonin between the light and dark phases in C57BL/6J mice. Moreover, plasma melatonin levels were below the detection limit of the assay in both phases and pineal melatonin was < 10% of that in C3H/HeJ mice. Bipedal ambulation for 40 wk in C57BL/6J mice induced scoliosis at a rate of 64.3%, and two of nine scoliotic mice showed two sites of spinal deformity. This type of ambulation in C3H/HeJ mice resulted in scoliosis at a lower rate (25%), and affected animals had only a single scoliotic site. However, PINX combined with bipedal ambulation in C3H/HeJ mice produced scoliosis at a rate (70%) similar to that seen in C57BL/6J mice, and some double deformations were induced. These results confirm our previous observations in rats, and also support our hypothesis that melatonin as well as the bipedal ambulation appear to play a critical pathogenic role in scoliosis in experimental mammals.