O-33 Cognitive dysfunction in mice with MuSK + myasthenia gravis

Abstract

Background Reports on cognitive dysfunction in muscle specific tyrosine kinase (MuSK) antibody seropositive myasthenia gravis (MG) patients, led us to study cognitive dysfunction in the MuSK + passive transfer MG (PTMG) model of mice. Methods Twelve 7-week-old female wild-type C57BL/6 J mice were passively immunized for 14 days with IgG from different MuSK + MG patients and 12 control mice were included into the study. Mice were evaluated with clinical, neurophysiological and behavioral tests [Barnes maze (BM) and novel object recognition (NOR)]. In the end of the study, the mice were euthanized, and muscles were immunostained to evaluate the postsynaptic membrane. Results Two-thirds of the immunized mice developed some myasthenic weakness (grade 0.5–2.0) and did not gain weight during the study. Four immunized mice revealed decrement on RNS on the day 15. In behaviour studies MuSK + PTMG mice spent less time exploring the novel object in the NOR test (MuSK + PTMG 36.4% ± 14.0 vs controls 52.4% ± 13.0, p = 0.02). On the contrary, the Barnes maze test could not demonstrate difference in spatial memory between the groups. Postsynapses of MuSK + PTMG mice were significantly more fragmented and lost their pretzel-shape in comparison to control mice (omohyoid muscle in MuSK + PTMG mice 3.3 ± 1.7 vs control mice 2.7 ± 1.4, p Conclusions We found that unrelated to muscle weakness and regardless of rodents’ innate preference of novelty, recognition memory was affected among MuSK + PTMG mice that provides support for the cognitive dysfunction among MuSK + MG patients.