During regeneration, axotomized neurons switch from a transmitting mode to a growth mode and express growth-associated proteins (Fu and Gordon, 1997). Labeling, electron microscope, and immunocytochemi-cal studies have shown that the materials for building new cell membrane and cytoskeleton in the elongating axon are supplied by an upregulation of RNA and protein synthesis in the neuron cell body (Grafstein, 1983) and the anterograde transport of the materials.
The growth cone signal transduction proteins, GAP-43 and CAP-23, the cytoskeletal proteins actin and tubulin, and cell adhesion molecules (CAMs) such as L1 and neural cell adhesion molecule (NCAM) are strongly upregulated, while choline acetyltransferase (CAT), the neurotransmitter substance P and neurofilament proteins are downregulated (Bisby, 1995; Fu and Gordon, 1997). The different proteins are transported distally at different rates. GAP-43 is transported rapidly, whereas G-actin and tubulin subunits are transported slowly (McQuarrie, 1983). There is a close correlation between the rate of transport of tubulin and actin and the rate of axonal regeneration (McQuarrie and Lasek, 1989). The radial maturation of regenerated axons is associated with the re-elaboration of neurofilaments (McQuarrie, 1983).
To regenerate successfully to their targets, sprouting neurons must survive and the endoneurial tubes must be able to provide optimal growth support. Neuron survival and axon elongation require both soluble and insoluble factors produced by immune cells and fibroblasts, target tissues, and the neurons themselves. The most important source of survival and elongation factors, however, is the Schwann cells of the endoneu-rial tubes, which dedifferentiate to a nonmyelinating support function during Wallerian degeneration.
Was this article helpful?