Hypoexcitability precedes denervation in the large fast-contracting motor units in two unrelated mouse models of ALS

被引:91
|
作者
Martinez-Silva, Maria de Lourdes [1 ]
Imhoff-Manuel, Rebecca D. [1 ]
Sharma, Aarti [2 ]
Heckman, C. J. [3 ,4 ,5 ]
Shneider, Neil A. [2 ]
Roselli, Francesco [6 ]
Zytnicki, Daniel [1 ]
Manuel, Marin [1 ,3 ]
机构
[1] Univ Paris 05, CNRS, Ctr Neurophys Physiol & Pathol, Paris, France
[2] Columbia Univ, Dept Neurol, Ctr Motor Neuron Biol & Dis, New York, NY USA
[3] Northwestern Univ, Dept Physiol, Feinberg Sch Med, Chicago, IL 60611 USA
[4] Northwestern Univ, Dept Phys Med & Rehabil, Feinberg Sch Med, Chicago, IL 60611 USA
[5] Northwestern Univ, Dept Phys Therapy & Human Movement Sci, Feinberg Sch Med, Chicago, IL 60611 USA
[6] Ulm Univ, Dept Neurol, Ulm, Germany
来源
ELIFE | 2018年 / 7卷
关键词
AMYOTROPHIC-LATERAL-SCLEROSIS; PLURIPOTENT STEM-CELLS; SPINAL MOTONEURONS; LUMBAR MOTONEURONS; IN-VIVO; NEURON DEGENERATION; SOD1; MICE; EXCITABILITY; DISEASE; HYPEREXCITABILITY;
D O I
10.7554/eLife.30955
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hyperexcitability has been suggested to contribute to motoneuron degeneration in amyotrophic lateral sclerosis (ALS). If this is so, and given that the physiological type of a motor unit determines the relative susceptibility of its motoneuron in ALS, then one would expect the most vulnerable motoneurons to display the strongest hyperexcitability prior to their degeneration, whereas the less vulnerable should display a moderate hyperexcitability, if any. We tested this hypothesis in vivo in two unrelated ALS mouse models by correlating the electrical properties of motoneurons with their physiological types, identified based on their motor unit contractile properties. We found that, far from being hyperexcitable, the most vulnerable motoneurons become unable to fire repetitively despite the fact that their neuromuscular junctions were still functional. Disease markers confirm that this loss of function is an early sign of degeneration. Our results indicate that intrinsic hyperexcitability is unlikely to be the cause of motoneuron degeneration.
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页数:26
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