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Cognitive dysfunction in mice with passively induced MuSK antibody seropositive myasthenia gravis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.
Catholic Univ, Dept Neurol, Rome, Italy.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rostedt Punga: Clinical Neurophysiology.ORCID iD: 0000-0002-2178-9413
2019 (English)In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 399, p. 15-21Article in journal (Refereed) Published
Abstract [en]

Recent reports on cognitive dysfunction, in addition to skeletal muscle fatigue, in muscle-specific tyrosine kinase antibody seropositive (MuSK+) myasthenia gravis (MG) patients led us to study cognition in mice with MuSK+passive transfer MG (PTMG). Twelve 7-week-old female wild-type C57BL/6J mice were passively immunized with IgG from MuSK+ MG patients and 12 control mice received intraperitoneal saline injections. Mice were evaluated with clinical, neurophysiological and behavioral tests (Barnes maze (BM) and novel object recognition (NOR)), and the muscles were immunostained to evaluate the neuromuscular junction in the end of the study. Two-thirds of the immunized mice developed clinically distinct MuSK + PTMG. MuSK + PTMG mice spent less time exploring the novel object in the NOR test (MuSK+ mice 36.4% +/- 14.0 vs controls 52.4% +/- 13.0, p = .02), unrelated to the muscle weakness and regardless of rodents' innate preference of novelty. In the BM test, control mice were more eager to use the direct strategy than the MuSK+ mice (MuSK+ 17.3% vs controls 29.5%, p = .02). Our findings shed new light on cognition dysfunction in human MuSK + MG patients and indicate that recognition memory in the perirhinal cortex could be affected in MuSK + MG.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2019. Vol. 399, p. 15-21
Keywords [en]
MuSK, Myasthenia, Mice, Cognitive dysfunction, Behavioral, Hippocampus
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-383198DOI: 10.1016/j.jns.2019.02.001ISI: 000465148900004PubMedID: 30738333OAI: oai:DiVA.org:uu-383198DiVA, id: diva2:1338650
Funder
Swedish Research Council, VR-523-2014-2048Available from: 2019-07-23 Created: 2019-07-23 Last updated: 2019-07-23Bibliographically approved

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Sabre, LiisRostedt Punga, Anna

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