Premium
ALS‐IgG‐induced selective motor neurone apoptosis in rat mixed primary spinal cord cultures
Author(s) -
Demestre M.,
Pullen A.,
Orrell R. W.,
Orth M.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03184.x
Subject(s) - amyotrophic lateral sclerosis , spinal cord , apoptosis , motor neuron , programmed cell death , medicine , immunology , primary culture , neuroscience , pathology , biology , cell culture , disease , biochemistry , genetics
There is evidence that in sporadic amyotrophic lateral sclerosis (ALS) immunological mechanisms may be involved in the pathophysiology of the disease. We tested whether purified IgG from ALS patients induce cell death in rat mixed primary spinal cord cultures and compared this with the effect of IgG purified from patients with Guillain–Barré syndrome (GBS) or from healthy donors. Treatment with ALS‐IgG increases caspase‐3 apoptosis when compared with control IgG or with GBS‐IgG, but does not induce death by necrosis. Because ALS is characterized by the selective loss of motor neurones, we next assessed the differential effect of ALS‐IgG on motor neurones or astrocytes. We showed, semiquantitatively, that motor neurones are more susceptible to apoptosis when cultures were treated with ALS‐IgG compared with control‐IgG. In conclusion, we have demonstrated in primary spinal cord cultures that IgG from patients with ALS induces apoptosis selectively in motor neurones, and that the caspase‐3 pathway is involved. This suggests that immunological mechanisms may contribute to the selective loss of motor neurones in ALS.