Renshaw cell loss in a transgenic mouse model of amyotrophic lateral sclerosis

The distribution and abundance of immunohistochemically‐identified Renshaw cells was studied in the lumbar spinal cord of an amyotrophic lateral sclerosis (ALS) mouse model. Transgenic G93A‐SOD1 mice displayed ALS‐like disease with the first neurological sign occurring at 90 days of age and progression at 100 to 150 days of age. Gephyrin and calbindin D28k immunofluorescence were used to identify and count the putative Renshaw cells in lumbar spinal cord tissue from mice at 40, 70, 90 and 145 days of age. Preliminary results suggest that in this model of ALS, functional neurological deficits are preceded and accompanied by a profound loss of gephyrin‐ and calbindin D28k labeled putative Renshaw cells. In 30 micron sections of lumbar spinal cord, mean counts per ventral horn were: at 40 days ALS=1.73 and control=3.13; at 70 days ALS=2.00 and control=3.32; and at 90 days ALS=2.22 and control=3.28; and at 145 days ALS=1.39 and control=3.08. Differences were significant (p<0.05; Mann‐Whitney Rank Sum test) for all ages. A significant decrease in number of Renshaw cells weeks prior to the onset of the disease suggests that, in the B6.Cg‐Tg(SOD1‐G93A)1Gur/J transgenic mouse model, the loss of motor‐related interneurons precedes clinical neurological deficit onset and progression of the disease and the loss of Renshaw interneurons occurs before the onset of motor neuron death. Supported by NIH 5R01HL075034‐05. Grant Funding Source : NIH