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 24h 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.
Jurasinski
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Department of Pediatrics H085, The Pennsylvania State University College of Medicine, Hershey, PA17033, USA.
Lieth
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Dang Do
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AN
Schengrund
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CL
D000818:Animals; D015153:Blotting, Western; D019274:Botulinum Toxins, Type A; D005455:Fluorescent Antibody Technique; D008297:Male; D008565:Membrane Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009411:Nerve Endings / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010243:Paralysis / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050825:Synaptosomal-Associated Protein 25
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D019274:Botulinum Toxins, Type A