Souayah Nizar, Sharovetskaya Anna, Kurnellas Michael P, Myerson Matthew, Deitch Jeffrey S, Elkabes Stella
Department of Neurology and Neuroscience, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103.
Department of Neurology, Drexel University College of Medicine, Philadelphia, PA.
Exp Neurol. 2008 Dec;214(2):341-346. doi: 10.1016/j.expneurol.2008.09.002. Epub 2008 Sep 19.
The potential of MUNE as a unique electrophysiological tool to detect early motor unit abnormalities during a clinically silent period was investigated in the plasma membrane calcium ATPase 2 (PMCA2)-heterozygous mice. There was a significant reduction in MUNE in the PMCA2-heterozygous mice as compared to the wild type littermates at two months of age. In contrast, the compound motor action potential (CMAP) was not altered. The conduction velocity (CV) of the sensory nerve and sensory nerve action potentials (SNAP) were not modified indicating lack of major sensory deficits. Interestingly, despite a decline in MUNE at this age, no changes were detected in choline acetyl transferase (ChAT) positive motor neuron number in the ventral horn of the lumbar spinal cord. Hindlimb grip strength, a test that evaluates clinical dysfunction, was also similar to that of the wild type controls. However, motor neuron number significantly decreased by five months suggesting that a drop in MUNE preceded motor neuron loss. In the two-month-old PMCA2-null mice, reduced MUNE measurements coincided with lower motor neuron number and decreased hindlimb grip strength. The fall in motor neuron number was already detectable at three weeks, the earliest time studied, and became more pronounced by five months. Our results show that even partial reductions in PMCA2 levels are sufficient to cause delayed death of motor neurons and that MUNE may be a reliable and sensitive approach to detect pathology prior to cell loss and in the absence of overt clinical signs.
在质膜钙ATP酶2（PMCA2）杂合小鼠中，研究了运动单位数目估计（MUNE）作为一种独特的电生理工具在临床无症状期检测早期运动单位异常的潜力。与野生型同窝小鼠相比，2月龄的PMCA2杂合小鼠的MUNE显著降低。相比之下，复合肌肉动作电位（CMAP）没有改变。感觉神经的传导速度（CV）和感觉神经动作电位（SNAP）没有改变，表明没有明显的感觉缺陷。有趣的是，尽管这个年龄段的MUNE有所下降，但在腰脊髓腹角中胆碱乙酰转移酶（ChAT）阳性运动神经元的数量没有变化。后肢握力测试评估临床功能障碍，其结果也与野生型对照相似。然而，到5个月时运动神经元数量显著减少，这表明MUNE的下降先于运动神经元的丧失。在2月龄的PMCA2基因敲除小鼠中，MUNE测量值降低与运动神经元数量减少和后肢握力下降同时出现。运动神经元数量的下降在研究的最早时间即3周时就已可检测到，到5个月时变得更加明显。我们的结果表明，即使PMCA2水平的部分降低也足以导致运动神经元的延迟死亡，并且MUNE可能是一种在细胞丢失之前且在没有明显临床体征的情况下检测病变的可靠且敏感的方法。
