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J Physiol. 2018 May 1;596(9):1723-1745. doi: 10.1113/JP275498. Epub 2018 Mar 26.

The vulnerability of spinal motoneurons and soma size plasticity in a mouse model of amyotrophic lateral sclerosis.

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Department of Neuroscience, Cell Biology, and Physiology, Boonshoft School of Medicine and College of Science and Mathematics, Wright State University, Dayton, OH, 45435, USA.
Department of Biomedical, Industrial, and Human Factors Engineering, College of Engineering and Computer Science, Wright State University, Dayton, OH 45435, USA.



Motoneuron soma size is a largely plastic property that is altered during amyotrophic lateral sclerosis (ALS) progression. We report evidence of systematic spinal motoneuron soma size plasticity in mutant SOD1-G93A mice at various disease stages and across sexes, spinal regions and motoneuron types. We show that disease-vulnerable motoneurons exhibit early increased soma sizes. We show via computer simulations that the measured changes in soma size have a profound impact on the excitability of disease-vulnerable motoneurons. This study reveals a novel form of plasticity in ALS and suggests a potential target for altering motoneuron function and survival.


α-Motoneuron soma size is correlated with the cell's excitability and function, and has been posited as a plastic property that changes during cellular maturation, injury and disease. This study examined whether α-motoneuron somas change in size over disease progression in the G93A mouse model of amyotrophic lateral sclerosis (ALS), a disease characterized by progressive motoneuron death. We used 2D- and 3D-morphometric analysis of motoneuron size and measures of cell density at four key disease stages: neonatal (P10 - with earliest known disease changes); young adult (P30 - presymptomatic with early motoneuron death); symptom onset (P90 - with death of 70-80% of motoneurons); and end-stage (P120+ - with full paralysis of hindlimbs). We additionally examined differences in lumbar vs. sacral vs. cervical motoneurons; in motoneurons from male vs. female mice; and in fast vs. slow motoneurons. We present the first evidence of plastic changes in the soma size of spinal α-motoneurons occurring throughout different stages of ALS with profound effects on motoneuron excitability. Somatic changes are time dependent and are characterized by early-stage enlargement (P10 and P30); no change around symptom onset; and shrinkage at end-stage. A key finding in the study indicates that disease-vulnerable motoneurons exhibit increased soma sizes (P10 and P30). This pattern was confirmed across spinal cord regions, genders and motoneuron types. This extends the theory of motoneuron size-based vulnerability in ALS: not only are larger motoneurons more vulnerable to death in ALS, but are also enlarged further in the disease. Such information is valuable for identifying ALS pathogenesis mechanisms.


ALS; motoneurons; soma size

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