Contribution of pineal hormone ; melatonin to the induction of experimental scoliosis in bipedal mice.

除了通过松果体切除术（PINX）诱导鸡脊柱侧凸外，我们之前已经证明，松果体切除术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。本研究使用遗传低循环褪黑素水平的C57BL/6J小鼠，主要目的是研究C57BL/6J小鼠双足行走对脊柱畸形的影响是否与去松果体的双足大鼠相同。本研究分为两个阶段。第一个实验的目的是确定C57BL/6J小鼠品系在明暗周期的明暗阶段是否确实表现出降低的血浆浓度和/或松果体褪黑素含量。第二个实验的目的是评估；(i) C57BL/6J小鼠单独双足行走是否会诱发脊柱侧弯，（ii）另一种小鼠品系（即C3H/HeJ）的PINX双足行走是否与C57BL/6J小鼠的褪黑激素合成和分泌的昼夜波动更大，与单独双足行走的效果相似。C3H/HeJ小鼠作为对照，与光照期相比，黑暗期的血浆浓度和松果体中褪黑素的含量均显著增加。相比之下，C57BL/6J小鼠在明暗阶段的循环水平和松果体中褪黑素含量没有差异。两期血浆褪黑素水平均低于检测限，松果体褪黑素< C3H/HeJ小鼠的10%。C57BL/6J小鼠双足行走40周后，脊柱侧凸发生率为64.3%，9只脊柱侧凸小鼠中有2只出现两处脊柱畸形。在C3H/HeJ小鼠中，这种类型的行走导致脊柱侧凸的发生率较低（25%），而且受影响的动物只有一个脊柱侧凸部位。然而，在C3H/HeJ小鼠中，PINX联合两足行走产生脊柱侧凸的比例（70%）与C57BL/6J小鼠相似，并诱导了一些双重变形。这些结果证实了我们之前在大鼠身上的观察结果，也支持了我们的假设，即褪黑激素和两足行走似乎在实验性哺乳动物脊柱侧凸中起关键的致病作用。少

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 exh … More ibits 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 weeks 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. Less