Changes in the neuromuscular synapse induced by an antibody against gangliosides.
In this study, we used a monoclonal IgM antibody from a patient with a pure motor chronic demyelinating polyneuropathy, which binds specifically to the complex gangliosides GM(2), GalNAc-GD(1a), and GalNAc-GM(1b), which appear to have a common epitope of -[GalNAcbeta1-4Gal(3-2alphaNeuAc)beta1]. This was done for the following reasons: (1) to localize these gangliosides in specific cellular components of the neuromuscular junction (NMJ), and (2) to describe the anti-ganglioside antibody-induced structural and functional changes in the NMJs to gain insight into the role of gangliosides in the synaptic function. Using immunofluorescence techniques, we found that these gangliosides are located only in the presynaptic component of the motor end-plates, both in nerve terminals and in Schwann cells. After 2 weeks of continued passive transfer of the IgM monoclonal antibody over the mouse levator auris longus muscle, electromyography showed an axonal or NMJ disorder. Morphology showed important nerve terminal growth and retraction changes. Using intracellular recording electrophysiology, we found neurotransmitter release alterations, including quantal content reduction and an immature expression of voltage-dependent calcium channels similar to what occurred during NMJ development and regeneration. These changes were complement independent. The results showed that these gangliosides were involved in the reciprocal Schwann cell-nerve terminal interactions, including structural stability and neurotransmission.
Santafé
Manel M
MM
Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, carrer St Llorenç #21, 43201 Reus, Spain.
Sabaté
M Mar
MM
Garcia
Neus
N
Ortiz
Nico
N
Lanuza
M Angel
MA
Tomas
Josep
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D005678:G(M2) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000145:classification / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D009121:Muscle Denervation / Q000379:methods; D016900:Neurofilament Proteins / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D050765:Qa-SNARE Proteins; D011950:Receptors, Cholinergic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D000911:Antibodies, Monoclonal; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005732:Gangliosides; D007075:Immunoglobulin M; D008565:Membrane Proteins; D016900:Neurofilament Proteins; D050765:Qa-SNARE Proteins; D011950:Receptors, Cholinergic; D009418:S100 Proteins; C051774:neurofilament protein H; D005678:G(M2) Ganglioside