Anti-synaptic antibody in allergic encephalomyelitis. II. The synapse-blocking effects in tissue culture of...

It has been suggested that demyelination cannot account for all of the observed clinical symptoms of multiple sclerosis (MS), in particular the rapidity of onset and remission of the disease, and attention has been focussed on the role of the synapse in 'demyelinating diseases'. In the present paper we have attempted to resolve the fundamental question of the site of action of a demyelinating disease, experimental allergic encephalomyelitis (EAE), by the use of cultures of neonatal rat cerebellum. Electrophysiological and morphological development in these cultures run hand-in-hand, and in the first few days in vitro there is a 4-5 day period when synapses are both seen ultrastructurally and known to be functioning but before the onset of myelination. The serum from guinea pigs with EAE was added to these cultures at different stages during their development and the morphological and electrophysiological effects observed. An abolitionary effect on the bioelectric activity of the culture was only observed when the serum was added to mature, myelinated cultures. Also the same active sera had no effect on synaptic activity before myelination had occurred. We conclude that the synaptic blocking effect occurs only when myelin is destroyed.