IN-VIVO IMAGING SHOWS LOSS OF SYNAPTIC SITES FROM NEUROMUSCULAR-JUNCTIONS IN A MODEL OF MYASTHENIA-GRAVIS

We examined the pre- and postsynaptic elements of the neuromuscular ju nction during immune attack on the postsynaptic acetylcholine receptor s (AChRs) in a model of myasthenia gravis (MG). We followed, in the st ernomastoid muscle of living mice, the staining of nerve terminals and postsynaptic AChRs at individual neuromuscular junctions in situ for up to 16 days after exposure to a monoclonal anti-AChR antibody. Sever al exposures to this antibody over 6 days led to spotty loss of AChR s taining 1 to 3 days later within individual neuromuscular junctions. I n addition, we observed loss of motor nerve terminal staining at presy naptic sites opposed to postsynaptic regions that had lost AChRs. Site s that lost pre- and postsynaptic staining were often immediately adja cent to other junctional regions that maintained a high density of ACh Rs and still stained presynaptically. Ultimately, the loss of synaptic sites resulted in neuromuscular junctions that appeared to be abnorma lly fragmented. To determine whether junctions recovered from the immu ne attack, we followed some antibody-treated muscle fibers for an addi tional 8 days without further exposure to antibody. Signs of recovery were evident because some of the synaptic regions that had previously lost AChRs subsequently regained them. But these junctions still remai ned fragmented both pre- and postsynaptically. These findings suggest that the postsynaptic membrane is affected in a highly local way by th e immune attack on AChRs occurring in MG. One consequence of this atta ck is a long-term loss of not only postsynaptic components but also th e overlying nerve terminals.