Correlation of cleavage of SNAP-25 with muscle function in a rat model of Botulinum neurotoxin type A induced paralysis

Injection of botulinum neurotoxin serotype A (BoNT/A) into muscle results in cleavage of the synaptosomal associated protein of 25 kDa (SNAP-25) and relatively long-term paralysis. However, nerve-terminal sprouting, which appears to require intact SNAP-25, has been reported to occur much earlier. The difference between the long-term paralysis induced by injection of BoNT/A and the short time needed for sprouting led us to investigate the relationship between BoNT/A catalyzed cleavage of SNAP-25 and muscle function. The effect of BoNT/A on SNAP-25 present in nerve endings innervating gastrocnemius muscles of rats was monitored over time. Cleaved SNAP-25 was found in nerve terminals innervating the muscles within 24 h of inoculation with BoNT/A and was present more than 2 months later. Comparison of the ratios of cleaved to intact SNAP-25 from the onset of BoNT/A-induced paralysis until function was regained indicated that paralysis was probable when the ratio of cleaved to intact SNAP-25 was greater than 0.35.