Neuromuscular paralysis and recovery in mice injected with botulinum neurotoxins A and C.

Abstract

Botulinum neurotoxin type A (BoNT/A) is commonly used in human therapy. This treatment may induce immunoresistance and preliminary evaluation of other botulinum neurotoxin serotypes suggested botulinum neurotoxin type C (BoNT/C) to be a good alternative to BoNT/A. Here, we have further characterized the biological activities of BoNT/C using a variety of experimental approaches. Muscle paralysis and time of recovery of mouse hind limb injected with BoNT/A or BoNT/C were assayed with the Digit Abduction Scoring assay. The extent and duration of paralysis were similar with the two toxin serotypes. Extensor digitorum longus or tibialis anterior muscles were dissected at times of complete paralysis and of complete recovery. Muscle weight and force were significantly reduced in mice injected with BoNT/A and BoNT/C, and some atrophy persisted for a long time. In BoNT/C-treated junctions, nerve terminal sprouting was prominent, indicating that the capacity to extend the field of innervation is not hampered by BoNT/C. BoNT/C induced a marked decrease in the frequency of miniature endplate potentials and in the amplitude of endplate potentials. 3,4-diaminopyridine reversed the effect of BoNT/C by increasing the amplitude of synchronized endplate potentials. The present study shows an extensive similarity in the biological activities of BoNT/A and BoNT/C, further supporting the suggestion that BoNT/C is a valid alternative to BoNT/A.

• Authors: Laura Morbiato, Luca Carli, Eric A Johnson, Cesare Montecucco, Jordi Molgó, Ornella Rossetto
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 25 Issue 9 Pg. 2697-704 (May 2007) ISSN: 0953-816X [Print] France
• PMID: 17561839 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuromuscular Blocking Agents
• Potassium Channel Blockers
• 4-Aminopyridine
• Botulinum Toxins
• Botulinum Toxins, Type A
• botulinum toxin type C
• Amifampridine

Topics

• 4-Aminopyridine (analogs & derivatives, pharmacology)
• Amifampridine
• Animals
• Botulinum Toxins (pharmacology, therapeutic use)
• Botulinum Toxins, Type A (immunology, pharmacology, therapeutic use)
• Drug Resistance (immunology)
• Excitatory Postsynaptic Potentials (drug effects, physiology)
• Male
• Mice
• Motor Neurons (drug effects, physiology)
• Muscle Contraction (drug effects, physiology)
• Muscle Weakness (chemically induced, metabolism, physiopathology)
• Muscle, Skeletal (innervation, physiopathology)
• Muscular Atrophy (chemically induced, metabolism, physiopathology)
• Neuromuscular Blockade (methods)
• Neuromuscular Blocking Agents (pharmacology, therapeutic use)
• Neuromuscular Junction (drug effects, metabolism, physiopathology)
• Neuronal Plasticity (drug effects, physiology)
• Organ Size (drug effects, physiology)
• Paralysis (chemically induced, metabolism, physiopathology)
• Potassium Channel Blockers (pharmacology)
• Presynaptic Terminals (drug effects, physiology)
• Recovery of Function (physiology)