Immunization of guinea pigs with human choline acetyltransferase induces selective lower motoneuron destruction

Abstract

Prior studies have demonstrated that guinea pigs immunized with bovine spinal motoneurons develop immune-mediated lower motoneuron disease. In the present experiments, guinea pigs immunized with choline acetyltransferase (ChAT) from human placenta develop lower motoneuron destruction and striated muscle atrophy. In this model, increased IgG was detected in lower motoneurons and at the motor end-plate by immunocytochemistry. Ultrastructural analysis revealed an increase in calcium content and in the density of synaptic vesicles in axon terminals at neuromuscular junctions. Similar morphological changes could be induced in mice following passively transfer of IgG from ChAT-immunized guinea pigs. The increased IgG uptake and raised calcium content in motor axon terminals as well as the selective lower motoneuron damage, suggest that a similar final common pathway can lead to motoneuron injury following immunization with human placental ChAT or bovine spinal motoneurons.