Neurons in the Peripheral Nervous System Can Regenerate Their Axons
The ability of PNS neurons to regenerate their axons contrasts sharply to damaged neurons in the CNS. This difference is due in large part to the role of trophic factors, which prevent the degeneration of peripheral neurons after axotomy. Recent discoveries have shown that some of the same molecules required for immature neurons to develop and survive are also involved in the survival of adult neurons after injury. What happens when the axons of adult sympathetic neurons are cut?
- If axons of postsynaptic neurons are cut, then presynaptic neurons withdraw their axon terminals.
- If exogenous NGF is added, then regeneration and reinnervation occurs.
- On the other hand, if anti-NGF antibodies are added to neutralize NGF, then regeneration is blocked.
- Moreover, if colchicine (which depolymerizes microtubules) is added to block the retrograde transport of NGF from the target cell to the damaged sympathetic neuron's cell body, then regeneration is inhibited.
Reactions of sympathetic neurons to injury:
Neuronal Regeneration
This section focuses on the serious, and often irreversible, damage to central and peripheral nervous systems caused by injury to neurons. In almost every case, neurons have withdrawn from the mitotic cycle and therefore can no longer divide to produce new neurons to replace damaged cells. Therefore, neuron loss due to injury has profound results, since the loss of affected pathways will permanently change the functional circuitry of the nervous system. In those cases where neurons do regenerate following injury, the mechanisms that contribute to regeneration appear to be very similar to the events that promote axon growth and synapse formation during development. Several general rules govern neuronal responses to injury:
- Regeneration in mammals is much poorer than lower vertebrates.
- Regeneration in the CNS is much less likely than in the PNS.
- Trophic factors play important roles in neuronal regeneration.
Neurons in the peripheral nervous system can regenerate their axons. This contrasts with the general inability of damaged neurons in the CNS to regenerate. The regeneration of peripheral neurons is due in large part to the role of trophic factors which provide an important function in preventing their degeneration after axotomy. Some of the same molecules required for immature neurons to develop and survive are also involved in the survival of adult neurons after injury. For example, if the axons of an adult sympathetic neuron are cut, the axon terminals of afferent neurons withdraw their axon terminals. However, if exogenous NGF is added, then regeneration and reinnervation occurs. If anti-NGF antibodies are added to neutralize NGF, then regeneration is blocked. Blocking the retrograde transport of NGF from the target cell to the damaged sympathetic neuron's cell body also inhibits regeneration. Thus, NGF is required for the regeneration and maintenance of peripheral synaptic connections in the adult PNS.
Schwann cells also contribute to the regeneration of peripheral axons. During damage and regeneration of axons, macrophages are activated and invade damaged areas. They secrete mitogenic factors that stimulate Schwann cell proliferation. Glial cell proliferation results in the increased secretion of extracellular matrix molecules and helps to promote adhesion between the regenerating axons and the remaining supporting cells. The synthesis and secretion of NGF is also stimulated under these conditions and provides important short-term conditions for regeneration. Thus, NGF plays another role in regeneration because it is produced by components of the peripheral nervous system that are not themselves postsynaptic targets.
