Sporadic amyotrophic lateral sclerosis: is SMN-Gemins protein complex of importance for the relative resistance of oculomotor nucleus motoneurons to degeneration?

Abstract

Lower motoneurons (MNs) show varied vulnerability in amyotrophic lateral sclerosis (ALS): those of non-ocular brainstem nuclei and most of those of the spinal cord are highly vulnerable, while those of extraocular brainstem nuclei are quite resistant. Results of our former study on the immunoexpression of the survival of motor neuron protein (SMN) and Gemins 2-4 in cervical spinal cord anterior horn -MNs of sporadic ALS patients suggested that arelative deficit in Gemin2 may play some role in the pathomechanism of the disease. Here, we tested this idea further by comparing immunoexpression patterns of SMN and Gemins 2-8 between MNs of the oculomotor nucleus and -MNs of the cervical spinal cord anterior horns in autopsy material from sALS patients and controls. In the latter, no considerable difference in any studied protein was found between these structures except that SMN expression was slightly but significantly lower (p < 0.01) in the oculomotor MNs. In the sporadic ALS patients, the expression of SMN, Gemin4 and Gemin7 was significantly weaker (p < 0.05, p < 0.05 and p < 0.01, respectively), while that of Gemin8 was stronger (p < 0.001) in the MNs of the oculomotor nucleus than in the examined cervical spinal cord anterior horn -MNs. The immunoexpression of Gemin3 and Gemin6 in the spinal cord correlated strongly negatively with ALS duration (Spearman's correlation coefficient: RS = -0.84, p < 0.001, and RS = -0.86, p = 0.002, respectively). In the oculomotor nucleus MNs, no studied protein immunoexpression correlated significantly with ALS duration, but there was atendency for such negative correlation for Gemin2 (RS = -0.56, p = 0.07). There was an apparent relative deficit of Gemin2 and Gemin8 in the spinal cord -MNs and of Gemins 2, 4 and 7 in the oculomotor nucleus MNs. These data do not support the hypothesis that the diverse ALS vulnerability of the two MN subsets is related to their disparate expression patterns of SMN and Gemins 2-8. The differences in these patterns may result from ALS-related epiphenomena, or from intrinsic differences in the structure and function between the MN subsets, or both.