Neurophysiological and immunohistochemical studies of IgG anti-GM1 monoclonal antibody on neuromuscular transmission: effects in rat neuromuscular junctions

• Published in: Neurological sciences Vol. 35; no. 2; pp. 205 - 213
• Main Authors: Hotta, Sayako, Nagaoka, Takumi, Taguchi, Kyoji, Nakatani, Yoshihiko, Utsnomiya, Iku, Masuda, Yutaka, Abe, Kenji, Yuki, Nobuhiro
• Format: Journal Article
• Language: English
• Published: Milan Springer Milan 01.02.2014; Springer Nature B.V
• Subjects: Action Potentials; Animals; Antibodies, Monoclonal - immunology; Autoantibodies - immunology; Cells, Cultured; Collagenases - metabolism; Diaphragm - drug effects; Diaphragm - physiology; G(M1) Ganglioside - immunology; Immunoglobulin G - immunology; In Vitro Techniques; Medicine; Medicine & Public Health; N-Acetylgalactosaminyltransferases - genetics; N-Acetylgalactosaminyltransferases - metabolism; Neurofilament Proteins - metabolism; Neurology; Neuromuscular Junction - physiology; Neuroradiology; Neurosciences; Neurosurgery; Oligodeoxyribonucleotides, Antisense - pharmacology; Original Article; Presynaptic Terminals - physiology; Psychiatry; Qa-SNARE Proteins - metabolism; Rats; Rats, Wistar; S100 Proteins - metabolism; Spinal Cord - physiology; Spontaneous muscle action potential; Neuromuscular junctions; Motor nerve; Anti-GM1 monoclonal antibody; GM1 epitope
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-013-1480-z

Guillain–Barré syndrome, which is a variant of acute inflammatory neuropathy, is associated with anti-GM1 antibodies and causes ataxia. We investigated the effects of IgG anti-GM1 monoclonal antibody (IgG anti-GM1 mAb) on spontaneous muscle action potentials in a rat spinal cord–muscle co-culture system and the localization of IgG anti-GM1 mAb binding in the rat hemi-diaphragm. The frequency of spontaneous muscle action potentials in innervated muscle cells was acutely inhibited by IgG anti-GM1 mAb. When cultures were pretreated with GM2 synthase antisense oligodeoxynucleotide, IgG anti-GM1 mAb failed to inhibit spontaneous muscle action potentials, demonstrating the importance of the GM1 epitope in the action of IgG anti-GM1 mAb. Immunohistochemistry of rat hemi-diaphragm showed that IgG anti-GM1 mAb binding overlapped with neurofilament 200 (NF200) antibodies staining, but not α-bungarotoxin (α-BuTx) staining, demonstrating that IgG anti-GM1 mAb was localized at the presynaptic nerve terminal. IgG anti-GM1 mAb binding overlapped with syntaxin antibody and S-100 antibody in the nerve terminal. After collagenase treatment, IgG anti-GM1 mAb and NF200 antibodies did not show staining, but α-BuTx selectively stained the hemi-diaphragm. IgG anti-GM1 mAb binds to the presynaptic nerve terminal of neuromuscular junctions. Therefore, we suggest that the inhibitory effect of IgG anti-GM1 mAb on spontaneous muscle action potentials is related to the GM1 epitope in presynaptic motor nerve terminals at the NMJs.