Uptake of immunoglobulin G from amyotrophic lateral sclerosis patients by motor nerve terminals in mice.
Clinical and experimental evidence support an autoimmune etiopathogenesis for amyotrophic lateral sclerosis (ALS). We have shown that local application of ALS-IgG onto nerve terminals induces dysfunction in transmission at the neuromuscular junction. It has been established that IgG and other circulating serum proteins can be taken up by motor nerve terminals, being immunolocalized in the soma where they accumulate following retrograde axonal transport. In the present study, we investigated the presence of human ALS and control IgG in the soma of mouse motoneurons. IgG was applied onto motor nerve terminals of mice by subcutaneous injections on the left levator auris longus muscle which is innervated by a branch of the facial nerve. After several injections, sections of the brainstem containing the facial nuclei were immunoprocessed to detect human IgG. For all IgG tested, motoneuron labeling was significantly more intense in the facial nucleus ipsilateral to the site of injection. In ALS-IgG-treated animals, ipsilateral labeling was significantly stronger than that found on the ipsilateral side of control IgG-treated animals. Our results are compatible with the concept that motoneurons preferentially take up, transport and/or accumulate ALS-IgG. Uptake of pathogenic antibodies by motoneuron terminals may play a role in the pathogenesis of motoneuron disease.
Fratantoni
S A
SA
Instituto de Biologia Celular y Neurociencias, Prof. Eduardo de Roberts, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
Dubrovsky
A L
AL
Uchitel
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OD
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology*; D000818:Animals; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008875:Middle Aged; D009046:Motor Neurons / Q000276:immunology*; D009411:Nerve Endings / Q000276:immunology*; D009469:Neuromuscular Junction / Q000276:immunology*
D007074:Immunoglobulin G