The effects of botulinum neurotoxin A induced muscle paresis during a critical period upon muscle and spinal cord development in the rat.

Abstract

The second postnatal week is a critical period in rat motor development. The expansion of corticospinal innervation coincides with elimination of polyneuronal innervation of muscles, onset of quadrupedal locomotion and refinement of muscle afferent input to the ventral horn. Such developmental events are believed to be activity-dependent. In the present study, muscle afferent activity was temporarily reduced by injecting distal forelimb muscles with botulinum toxin A (BTX). Injections of toxin or saline were made unilaterally on postnatal day (P) 7 which in BTX-treated animals lead to a profound loss of movement in the affected limb over the next week before function returned. The neural tracer cholera toxin B (CTB) was injected into the extensor digitorum communis (EDC) at either P14 or P28. Allowing 3 days for tracer transport, the spinal cords were sectioned and immunostained for CTB and cJun. In separate experiments, behavioural testing of the forelimb was carried out between P35 and P49. Then, sections of EDC muscle were immunostained for slow myosin. An increased density of ventral horn muscle afferent boutons was observed at P17 in BTX-treated animals compared to controls, however, by P31, this difference was not significant. However, CTB labelling also revealed significantly increased motor axon terminals in the ventral Renshaw cell region in BTX-treated animals at P31, accompanied by raised expression of cJun in ipsilateral motoneurones. BTX-treated animals showed deficits in ladder walking, and their muscles contained a higher density and significantly more clustering of slow myosin expressing muscle fibres than controls. Temporary reduction in activity did not significantly alter muscle afferent development, but temporary blockade of neuromuscular junctions did affect both muscle and motor axon, in the longer term.

• Authors: Gavin J Clowry, Lauren Walker, Pattina Davies
• Journal: Experimental neurology (Exp Neurol) Vol. 202 Issue 2 Pg. 456-69 (Dec 2006) ISSN: 0014-4886 [Print] United States
• PMID: 16928374 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neurotoxins
• Parvalbumins
• Proto-Oncogene Proteins c-jun
• Cholera Toxin
• Choline O-Acetyltransferase
• Botulinum Toxins, Type A

Topics

• Age Factors
• Animals
• Animals, Newborn
• Behavior, Animal
• Botulinum Toxins, Type A (pharmacology)
• Cholera Toxin (metabolism)
• Choline O-Acetyltransferase (metabolism)
• Critical Period, Psychological
• Functional Laterality
• Immunohistochemistry (methods)
• Motor Neurons (drug effects, metabolism)
• Muscle Development (drug effects, physiology)
• Neurotoxins (pharmacology)
• Parvalbumins (metabolism)
• Proto-Oncogene Proteins c-jun (metabolism)
• Psychomotor Performance (drug effects, physiology)
• Rats
• Spinal Cord (drug effects, physiology)