Ultrastructural analysis of spinal motoneurones from mice treated with IgGfrom ALS patients, healthy individuals, or disease controls

Reports that ALS-IgG injected into mice results in ultrastructural abnormal ities and enhanced deposition of Ca2+ in their spinal motoneurones are unve rified. To obtain verification, affinity purified IgG's from ten healthy su bjects, seventeen ALS patients and eight disease controls (eg cases of LEMS , MS,) were injected into groups of mice in 4 daily doses by either i/m inj ection, or i/p (Total doses, 2-4 mg i/p, I mg i/m). Immunocytochemistry ide ntified human IgG in lumbar motoneurones 48 h after the final dose. Their m orphology was examined by EM and intraneuronal Ca2+ was revealed by oxylate -pyroantimonate histochemistry and its identity verified by 2 degrees emiss ion spectroscopy. In the EMI motoneurones of non-injected mice, and mice re ceiving healthy IgGs had a lucent cytoplasm, intact mitochondria, and Golgi complexes comprising stacks of narrow ER. About 40% of Nissl bodies compri sed alternate rER lamellae and polyribosome arrays (Type 1 structure): 10% formed polyribosome clusters (Type 3). Mitochondria, Golgi ER and presynapt ic terminals contained Ca2+ associated pyroantimonate. I/m and i/p ALS-IgG produced similar results. Some ALS IgGs (i.e. patients) produced electron d ense degenerative cytology: all promoted fragmented and distended Golgi ER, polyribosmal hyperplasia, reduced numbers of Type I but raised numbers of Types 2 and 3 Nissl bodies, and a greater proportion of Golgi ER and presyn aptic terminals containing Ca2+-antimonate. With 4/8 disease control IgGs m otoneurones had normal Golgi and Nissl body organisation but dilated rER. C a2+ content was normal. Remaining IgGs produced normal ultrastructure. Resu lts support claims that ALS-IgG may be cytotoxic, and that it enhances the Ca2+ content of motoneurones and synaptic terminals. (C) 2000 Elsevier Scie nce B.V. All rights reserved.