9 Neurotrophism

9.1 Introduction

9.2 Trophic effects

•  Motor neurons exert a long term regulation over the physiological and metabolic properties of all the myofibres in a motor unit. This is often called the trophic effect of nerve on muscle. The word trophic implies something of a nutritive effect, as if the nerve was feeding the muscle, but its current usage sometimes includes possible non‑nutritive effects such as the frequency patterns of nerve impulses to the muscle. The idea nerves might have a trophic function is far from new, and probably originates from ancient observations on the degenerative fate of denervated organs.
  
• All myofibres in the same motor unit have the same histochemical properties - because they are all innervated by the same motor neuron.  This is true for our meat animals, but not for other species such as lobsters.
  
• Trophic effects may be bi‑directional and sometimes the muscle has an influence on its motor neuron. For example, connections on the perikaryon (presynaptic terminal boutons) are lost when axons are cut, and they are restored when neuromuscular contact is re‑established. Similarly, growth-regulating substances may pass from muscle to nerve. 
• Denervation by cutting the axon linking the motor neuron to its myofibres removes the trophic effect - and the myofibres wither away (atrophy).
  

9.3 Crossed-reinnervation experiments

When axons are cut they can grow back to their motor unit - probably by the same mechanisms they first used to grow out to, and innervate the myofibres. Thus, a denervated motor unit can be restored to almost normal function if its axon is able to reconnect. In a reinnervation experiment two muscles are selected in the limb of an animal - one is dominated by slow-contracting myofibres and the other by fast-contracting myofibres. The nerves to these two muscles are cut and allowed to grow back.  We check normal function returns.  The slow muscle is still slow, and the fast muscle is still fast.  Gaining confidence with the technique we then attempt a crossed-reinnervation experiment.  The two nerves are cut and crossed over. The slow nerve is connected to the fast muscle.  The fast nerve is connected to the slow muscle. What happens?  When the axons grow back, they cannot find their original myofibres. Instead, they reinnervate the myofibres they can find.  The slow muscle then becomes fast-contracting, and the fast muscle become slow-contracting. The transformation is often imperfect but enough for all to agree there has been a change in contraction speed.

• The nerves  normally innervating fast muscles may differ from those normally innervating slow muscles in two general ways: (1) in the physical or chemical nature of the trophic factor they might deliver, and (2) in the frequency profile of the impulses they normally convey. These two possibilities are as difficult to separate as the effects of denervation and disuse. There is independent evidence for both, but they might also be interdependent.  For example, impulse frequency might influence the rate of delivery of trophic substances .
•  Similar results to those of crossed reinnervation experiments may be obtained by the transplantation of muscles.  A fast muscle regenerates in the original location of a slow muscle and vice versa. This confirms the validity of crossed-reinnervation experiments.
  

9.4 Axoplasmic flow

Trophic factors appear to be released from nerve terminals, often at a great distance from the perikaryon. But where are trophic substances produced in the neuron? Motor axons grow towards their muscles when neuromuscular relationships are first established and this involves a great increase in axoplasmic volume. The source of new axoplasm in the perikaryon is sufficient to allow repeated regeneration of transected axons, no matter how often they are cut back. If axons are constricted by a tight external ring or "bottleneck", the movement of axoplasm down the axon causes a bulge to develop proximal to the constriction. Distally, the axon becomes narrower because of a reduction of the axoplasmic flow. Thus, there is an axoplasmic flow along axons away from the perikaryon and axoplasmic flow is somehow involved with neurotrophic effects. 

•  Axoplasmic flow in mature axons is a bi-directional process with both slow (1 mm/day) and fast (400 mm/day) streams.
•  Slow transport probably accounts for the growth and regeneration of axons since the amount of material conveyed by slow transport greatly exceeds that carried by fast transport.
•  Fast transport is channeled in some way by microtubules or vesicles in the axon, and is sensitive to oxygen and temperature levels.  Colchicine disrupts microtubules and interferes with axoplasmic flow. It causes muscles to exhibit some of the features of denervation.
  
•  Slow transport carries mostly high molecular weight soluble proteins, while fast transport carries particles and a small amount of soluble protein. 

9.5 Activity patterns

One of the great difficulties of investigating neurotrophism is fast nerves exhibit burst of intense activity while slow nerves exhibit continuous low levels of activity.  Think of your own body movements, You use your fast muscles to do something vigorous  now and again, while you use your slow muscles continuously for breathing and posture.  Experimentally changing these activity patterns by blocking all normal activity and superimposing artificial activity from a programmed stimulator may also change myofibre metabolism.

9.6 Changes During Growth

1. Splayleg piglets.  Piglets are very vulnerable just after farrowing. The sow is likely to sit on them and crush them if they cannot move out of her way. Movement requires fully functional limbs.  If the hindlimbs splay outwards, locomotion is impossible. What normally holds the hindlimbs together? Answer - the medial adductor muscles. Immediately after farrowing there should be a rapid recruitment of postural myofibres. Intermediate myofibres are converted to red myofibres.  This does not happen in splayleg piglets. The hindlimbs should be loosely tied together with twine. This enables the piglets to scrabble along and survive until adductor muscle function becomes adequate.
2. Rapid muscle growth in young animals.   Rapid muscle growth (highly desired by producers) occurs because white myofibres exhibit faster increase in size (myofibre hypertrophy) than intermediate or red myofibres. ALSO, intermediate myofibres are converted to white myofibres.
3. Slow muscle growth in fat animals.  Slow muscle growth in the finishing period (highly desired by consumers who like tasty, succulent meat) occurs because of the increasing postural demands placed on major locomotory muscles. The animal has become fat and heavy.  It no longer leaps around like a baby.  It is slow moving.  Intermediate myofibres are converted to red myofibres. This is why meat from older animals is dark in colour (higher myoglobin) and strong in taste (more lipid).
4. White meat in poultry.  Chickens and turkeys evolved from heavy, grain-eating birds.  They only used flight to escape from predators.  For this they require massive, powerful wing muscles. Thus, chickens and turkeys are genetically programmed to develop breast muscles dominated by white myofibres derived from both secondary fibres AND myotubes.  This is the only case where we find myotubes becoming white myofibres.

Further information.

Trivia