Fig. 3

Activated c-Abl Accumulates in Human ALS Upper and Lower Motor Neurons. a Many pyramidal neurons (hatched arrows) in ALS motor cortex showed conspicuous accumulation of phosphorylated c-Abl (brown, cresyl violet counterstained). Some pyramidal neurons seen by cresyl violet had low or negative active c-Abl staining. The neuropil also showed immunoreactivity. b In control motor cortex, phosphorylated c-Abl (brown, cresyl violet counterstaining) was much less evident in pyramidal neuron cell bodies (hatched arrows) and in the neuropil compared to ALS motor cortex shown in A. Inset shows control motor cortical pyramidal neurons rich in Nissl substance and no active c-Abl immunoreactivity in the nucleus. c Phosphorylated c-Abl (brown, cresyl violet counterstaining) was localized to the nucleus of pyramidal neurons (hatched arrows) in ALS motor cortex and was sometimes seen as discrete nuclear inclusions. d Counts of motor cortical neurons positive for phosphorylated c-Abl in control (n = 8) and ALS (n = 16) cases. Values are mean ± SD. *p < 0.001. e, f Spinal cord motor neurons (hatched arrow) at pre-attritional (not shrunken) stages of degeneration in ALS cases [63] (E, hatched arrow) were strongly positive for phosphorylated c-Abl (brown, cresyl violet counterstain). In control spinal motor neurons (F, hatched arrow) c-Abl immunoreactivty (brown, cresyl violet counterstain) was nearly inconspicuous, even though some surrounding glial cells were positive. g Spinal cord motor neurons (hatched arrow) at advanced attritional stages (shrunken) of degeneration in ALS cases [63] (hatched arrow) were strongly positive for phosphorylated c-Abl (brown, cresyl violet counterstain). Subsets of glial cell nucleus were c-Abl-positive (open arrow). h Counts of spinal cord ventral horn neurons positive for phosphorylated c-Abl in control (n = 8) and ALS (n = 16) cases. Values are mean ± SD. *p < 0.001. Scale bars (in μm) = 24 (A, same for B), 10 (B inset), 8 (C), 130 (E, same for F), 8 (G)