Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALS
Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALS
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DOI：
10.1016/j.nbd.2005.06.019
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发表时间：
2006-01-01
影响因子：
6.1
通讯作者：
Maragakis, NJ
中科院分区：
文献类型：
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作者：
Lladó, J;Haenggeli, C;Maragakis, NJ
转基因突变超氧化物歧化酶（SOD 1）小鼠和大鼠一直是试图了解运动神经元病理学和变性的重要工具，但尚未研究该模型中死亡背后的机制。我们研究了突变体SOD1大鼠颈部运动神经元和膈神经的电生理和病理特性，并证明运动神经元丢失、膈神经复合肌肉动作电位振幅的进行性降低、膈神经纤维丢失和膈肌萎缩表明呼吸功能不全是导致SOD1大鼠死亡的重要因素。与以前的观察表明，在小鼠模型的疾病可能会发生回死的过程，我们没有观察到近端和远端轴突损失之间的差异，在膈神经的SOD1大鼠。这可能反映了呼吸运动神经元生物学的独特特征，或者可能与大鼠模型中与小鼠SOD1模型相比相对快速的下降过程有关。在腰骶脊髓中也观察到显著的运动神经元丢失，而在颅核中运动神经元相对保留。总而言之，这些数据表明呼吸运动神经元的丧失会导致显着的电生理变化和横膈萎缩。这些变化可能在导致这些动物死亡中起重要作用。(c)2005年爱思唯尔公司All rights reserved.
The transgenic mutant superoxide dismutase (SOD1) mice and rats have been important tools in attempting to understand motor neuron pathology and degeneration but the mechanism behind death in this model has not been studied. We studied the electrophysiologic and pathologic properties of the cervical motor neurons and phrenic nerves in mutant SOD1 rats and demonstrated motor neuron loss, progressive reduction of phrenic nerve compound muscle action potential amplitudes, phrenic nerve fiber loss, and diaphragm atrophy suggesting respiratory insufficiency as a significant contributing factor leading to SOD1 rat death. Unlike previous observations suggesting that a dying-back process may be occurring in the mouse model of the disease, we did not observe differences between proximal and distal axon loss in phrenic nerves of SOD1 rats. This may reflect a unique feature of respiratory motor neuron biology or may be related to the relatively rapid course of decline in the rat model when compared with the mouse SOD1 model. Significant motor neuron loss was also noted in the lumbosacral spinal cord with relative sparing of motor neurons in the cranial nuclei. Taken together, these data suggest that respiratory motor neuron loss results in significant electrophysiologic changes and diaphragmatic atrophy. These changes may play a significant role resulting in death of these animals. (c) 2005 Elsevier Inc. All rights reserved.