Gangliosides and anti-ganglioside antibodies in neuromuscular synaptic function

Abstract

The Guillain-Barr_ syndrome (GBS) is an acute, post-infectious neuropathy. Several clinical presentations are known, but general symptoms are symmetric muscle weakness and loss of tendon reflexes. In more than half of the GBS patients, antibodies against gangliosides can be detected in their serum. Gangliosides are glycosphingolipids, which are located in the outer layer of cell membranes, and play a role in cell-cell recognition and communication. Because gangliosides are highly enriched in the presynaptic nerve membranes, a role in synaptic transmission and the process of neurotransmitter release is assumed. We explored the physiological role of these gangliosides in transmitter release in neuromuscular synapses of mice using electrophysiological techniques. Furthermore, these synapses were also studied for the pathophysiological effects caused by antibodies against the gangliosides. The results show that gangliosides appear not to be fundamental for neuromuscular function, but rather have a modulating role. In addition, blocking of the complement system, using complement-component C5-inhibitors, is an effective method to protect the nerve membrane against the damaging effects of the activated complement system as a result of anti-ganglioside antibody binding. These and other experimental findings of this thesis are discussed in view of the current literature and the pathogenesis and therapeutical aspects of GBS.