Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice.
Pre- and postsynaptic changes in the neuromuscular junction in dystrophic mice.
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DOI：
10.3389/fphys.2015.00252
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发表时间：
2015
影响因子：
4
通讯作者：
Lovering RM
中科院分区：
文献类型：
--
作者：
Pratt SJP;Valencia AP;Le GK;Shah SB;Lovering RM
杜氏肌营养不良症（DMD）是一种破坏性的神经肌肉疾病，其中虚弱，对肌肉损伤的易感性增加，以及修复不足似乎是病理学的基础。虽然大多数注意力集中在肌纤维内，但我们最近在mdx小鼠（DMD小鼠模型）中证明了神经肌肉接头（NMJ）运动终板的显著形态学改变和损伤后相应的NMJ传递失败。在这里，我们扩展这些初步观察运动终板，以了解前与突触后形态，以及健康（WT）与mdx小鼠的突触下核。我们量化了成年小鼠终末神经的不连续性和分支。我们报告mdx和年龄依赖性变化的不连续性和增加分支相比，野生型。为了检查mdx和年龄依赖性的变化，在突触前和突触后结构的相对定位，我们计算NMJ占用率，定义为突触前囊泡与底层运动终板的足迹所占的比例。在mdx小鼠中，突触前和突触后形态之间的正常一致性偶联被改变，与年龄无关。最后，我们发现核的数量几乎增加了两倍，并增加了密度（核/面积）的NMJ。这些结果表明营养不良进展期间NMJ的实质性重塑。这种重塑反映了NMJ结构的突触前和突触后贡献者的可塑性，因此也可能是NM传输和肌肉功能。
Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease in which weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology. While most attention has focused within the muscle fiber, we recently demonstrated in mdx mice (murine model for DMD) significant morphologic alterations at the motor endplate of the neuromuscular junction (NMJ) and corresponding NMJ transmission failure after injury. Here we extend these initial observations at the motor endplate to gain insight into the pre- vs. postsynaptic morphology, as well as the subsynaptic nuclei in healthy (WT) vs. mdx mice. We quantified the discontinuity and branching of the terminal nerve in adult mice. We report mdx- and age-dependent changes for discontinuity and an increase in branching when compared to WT. To examine mdx- and age-dependent changes in the relative localization of pre- and postsynaptic structures, we calculated NMJ occupancy, defined as the ratio of the footprint occupied by presynaptic vesicles vs. that of the underlying motor endplate. The normally congruent coupling between presynaptic and postsynaptic morphology was altered in mdx mice, independent of age. Finally we found an almost two-fold increase in the number of nuclei and an increase in density (nuclei/area) underlying the NMJ. These outcomes suggest substantial remodeling of the NMJ during dystrophic progression. This remodeling reflects plasticity in both pre- and postsynaptic contributors to NMJ structure, and thus perhaps also NM transmission and muscle function.