期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 596, 期 9, 页码 1723-1745出版社
WILEY
DOI: 10.1113/JP275498
关键词
motoneurons; soma size; ALS
资金
- US National Institute of Health National Institute of Neurological Disorders and Stroke (NIH-NINDS) grant [NS091836]
alpha-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 alpha-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 alpha-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.
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