title: Repeated stimuli for axonal growth causes motoneuron death in adult rats: the effect of botulinum toxin followed by partial denervation.
abstract: Axons of motoneurons to tibialis anterior and extensor digitorum longus muscles of adult rats were induced to sprout by injecting botulinum toxin into them, by partial denervation or by a combination of the two procedures. Ten weeks later, the number of motoneurons innervating the control and operated tibialis anterior and extensor digitorum longus muscles was established by retrograde labelling with horseradish peroxidase. In the same preparations, the motoneurons were also stained with a Nissl stain (gallocyanin) to reveal motoneurons in the sciatic pool. Examination of the spinal cords from animals treated with botulinum toxin showed that the number of retrogradely labelled cells and those stained with gallocyanin in the ventral horn on the treated compared to the control side was unchanged. In rats that had their L4 spinal nerve sectioned on one side, the number of retrogradely labelled cells on the operated side was 48+/-3% (n = 5) of that present in the control unoperated ventral horn. Thus, just over half the innervation was removed by cutting the L4 spinal nerve. Counts made from gallocyanin-stained sections showed that 94+/-4% (n = 5) of motoneurons were present in the ventral horn on the operated side. Thus, section of the L4 spinal nerve did not lead to any death of motoneurons. In rats that had their muscles injected with botulinum toxin three weeks prior to partial denervation, the number of retrogradely labelled cells was reduced from 48+/-3% (n = 5) to 35+/-4% (n = 5). Moreover, only 67+/-5% (n = 5) of motoneurons stained with gallocyanin, suggesting that a proportion of motoneurons died after this combined procedure. This result was supported by experiments in which motor unit numbers in extensor digitorum longus muscles were determined by measurements of stepwise increments of force in response to stimulation of the motor nerve with increasing stimulus intensity. In partially denervated extensor digitorum longus muscles, 16.6+/-0.7 (n = 5) motor units could be identified, and in animals treated with botulinum toxin prior to partial denervation only 13.3+/-0.9 (n = 3) motor units were present. Taken together, these results show that treatment with botulinum toxin followed by partial denervation causes motoneuron death in adult rats.
authors.affiliation: Department of Anatomy and Developmental Biology, Centre for Neuroscience, University College London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: White
authors.forename: L
authors.initials: L
authors.lastname: Greensmith
authors.forename: G
authors.initials: G
authors.lastname: Vrbová
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D019274:Botulinum Toxins, Type A / Q000494:pharmacology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D005260:Female; D006614:Hindlimb; D007537:Isometric Contraction; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation; D010243:Paralysis / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019274:Botulinum Toxins, Type A