Sprouting capacity of lumbar motoneurons in normal and hemisected spinal cords of the rat

Abstract

Nerve sprouting to reinnervate partially denervated muscles is important in several disease and injury states. To examine the effectiveness of sprouting of active and inactive motor units (MUs) and the basis for a limit to sprouting, one of three rat lumbar spinal roots was cut under normal conditions and when the spinal cord was hemisected at T12. Muscle and MU isometric contractile forces were recorded and muscle fibres in glycogen-depleted single muscle units enumerated 23 to 380 days after surgery. Enlargement of intact MUs by sprouting was effective in compensating for up to 80% loss of innervation. For injuries that removed >70-80% of the intact MUs, muscle contractile force and weight dropped sharply. For partial denervation of <70%, all MUs increased contractile force by the same factor in both normally active muscles and muscles whose activity was reduced by T12 hemisection. Direct measurements of MU size by counting glycogen-depleted muscle fibres in physiologically and histochemically defined muscle units, provided direct evidence for a limit in MU size, whether or not the activity of the muscles was reduced by spinal cord hemisection. Analysis of spatial distribution of muscle fibres within the outer boundaries of the muscle unit demonstrated a progressive increase in fibres within the territory to the limit of sprouting when most of the muscle unit fibres were adjacent to each other. We conclude that the upper limit of MU enlargement may be explained by the reinnervation of denervated muscle fibres by axon sprouts within the spatial territory of the muscle unit, formerly distributed in a mosaic pattern.

Reinnervated muscle fiber type-grouping-inevitable?

“…This pattern of progressive muscle fiber type and MU muscle fiber clumping in the large reinnervated muscles is the same as the pattern that was observed and described in both large and small muscles after sprouting in partially denervated muscles [5, 7]. The clumping emerges as the regenerating nerves branch close to the denervated muscle fibers and the intact nerve fibers in partially denervated muscles emit sprouts to reinnervate adjacent muscle fibers.…”

Differential roles of α-, β-, and γ-actin in axon growth and collateral branch formation in motoneurons

“…Actin dynamics appears particularly important for axon arborization in motoneurons, as motor axons establish several thousand branches, each innervating a neuromuscular endplate ( Hirokawa et al, 1989 ). Axonal sprouting as a specific form of arborization plays a major role in the plasticity of motor units ( Tam and Gordon, 2003 ; Gordon and Tyreman, 2010 ). In the early stages of motoneuron disease, sprouting can compensate for loss of motoneurons and delay disease onset, as shown in a model of type III spinal muscular atrophy (SMA; Crawford and Pardo, 1996 ; Simon et al, 2010 ).…”

Compensatory axon sprouting for very slow axonal die‐back in a transgenic model of spinal muscular atrophy type III

“…Hence, the sprouting effectively compensated for the loss of the innervation by a proportion of motoneurons in the Smn +/− III transgenic mice. It is likely that the sprouting resulted in some but not extensive fibre‐type clumping in the partially denervated muscles because clumping becomes obvious only after extensive partial denervation (Gordon & Tyreman, ).…”