Immunological approach to the study of neurohumoral sleep factors: Effects on REM sleep of antibodies to brain stem proteins

Abstract

Proteins were collected for several months from the reticular formation of some 40 cats. The sodium dodecyl sulfate electrophoretic profile showed eight visible bands. Rabbits were inoculated with these proteins four times at weekly intervals in order to produce antibodies. Antibodies were also produced against cat serum proteins and cat serum albumin. These antibodies were tested for their effects on the sleep-wake cycle of another group of cats. The results of these experiments showed that the anti-reticular formation (MRF) antibodies and not antiserum or antialbumin antibodies, produced a specific decrease in rapid eye movement (REM) sleep without altering slow-wave sleep. It was also observed that when the anti-MRF antibodies were incubated with MRF proteins, the effect was lost, but that it persisted when they were incubated with serum protein only. It was also noted that the reduction in REM sleep was the result of an increase in the latency and a decrease in the frequency of REM periods, rather than in the duration of individual periods. In addition, the antibodies decreased some of the phasic elements of REM sleep such as multiple-unit and eye movement bursts. These experiments present the first direct evidence suggesting that specific protein molecules play an important role in triggering REM sleep.