9 Neurotrophism

9.1 Introduction

We have seen how myoblasts fuse to form multinucleate myofibres containing contractile myofibrils. A key point was the first myoblasts fused to form myotubes in the centres of their fasciculi (bundles of myofibres) while later myoblasts fused to form secondary fibres towards the outside of their fasciculi. In the pig, we saw how the myofibres located centrally in their fasciculi were likely to be slow-contracting myofibres with strong aerobic activity, while myofibres located on the outside were likely to be fast-contracting with strong anaerobic activity.

Thus, in the pig, myotubes are likely to develop into myofibres with slow-contraction and strong aerobic activity while secondary fibres develop fast-contraction and strong anaerobic activity.  This is generally true, but subject to modifications considered in this lecture.

Neurotrophism is one of the names used for the control of myofibre metabolism (both contraction speed and the balance of aerobic and anaerobic metabolism). Thus, neurotrophism is important in explaining muscle development. But first some questions.

Why is muscle fibre metabolism important for understanding meat production? Because fast-contracting myofibres exhibit fast growth, which means rapid meat production and high meat yields. And because slow-contracting myofibres are associated with taste and juiciness - which are obviously important in understanding meat quality.

Why do we use the pig as a model?  Because in the other species of meat animals the different types of myofibres do not maintain their positions in the fasciculi - their arrangement gets randomized and it is difficult to see what types of myofibres are derived from myotubes and secondary fibres.  The reason why the pig is so neat and tidy in this respect is unknown.  Historically, it gave animal scientists an advantage over biomedical scientists working with other animals - and we were able to make some useful contributions in this field using the pig as our model. Perhaps it was no accident the great German histologist, Theodore Schwann, used pigs as his material for proving animal bodies are composed of cells (the Cell Theory is now so obvious and widely accepted we forget what a major discovery it was). This is why he had to investigate the origin of skeletal muscle - because myofibres were the only cells of the body with many nuclei.  His theory was the body is divided into cells - each with one nucleus. Thus, he had to explain the special case of multinucleate myofibres - and he did so brilliantly, showing this was a special case where cells had fused together.

9.2 Trophic effects

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.

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. 

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

Histochemical types are important in meat animals because they are related to muscle growth and meat quality. Histochemical types also react differently during the conversion of muscles to meat, because they contain different levels of glycogen and anaerobic enzymes. Before it became known that myofibres could change from one type to another, growth-related changes in fibre types were not adequately controlled in agricultural experiments using myofibre histochemistry. Be very critical of any research paper assuming fibre types are constant regardless of animal age!

 This three dimensional plot shows changes in myofibre histochemistry during muscle growth in a pork muscle. In the bottom right corner, a population of fast-contracting myofibres (alkaline ATPase +) which are also anaerobic (anaerobic +) is changing to develop more aerobic activity (from 0 to + aerobic). Then their speed of contraction decreases (from 0 to + for acid-stable ATPase and from + to 0 for alkaline ATPase).   This type of change happens in older pigs as they become fatter. The initially white muscles along the loin develop more pigmentation as progressively more time is spent in postural work. Thus, meat from old pigs is  more pigmented than meat from younger pigs. This is true for many meat animals.  Thus, beef is more pigmented than veal, and mutton is more pigmented than lamb.

Here are some important examples of growth-related changes in meat production.
  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.

Structure and Development of Meat Animals and Poultry. Pages 324-336. Trophic effect of nerves.


The first crossed re-innervation experiments were undertaken in late Victorian times - but the researchers failed to notice the change in contraction speed. The subject started up again in the 1940s to help with nerve regeneration in young soldiers.The transformation of  histochemical types of myofibres is declining in research popularity - which is a good thing in my opinion.  Most researchers relied too heaving on subjective typing of myofibres (it's not real science unless you can measure it quantitatively!) and totally ignored the way intrafascicularly terminating myofibres can bias the data. The last blue diagram is where I quit the field 20 years ago.