Schwann cell degeneration

It is noteworthy that the axonal degeneration that occurs in the PNS of MAG-null mice is not observed in the CNS, possibly because other CNS myelin proteins enhance axonal stability. These could include PLP and/or CNP, both of which are needed for axonal stability in the CNS where they are present in much higher concentration. In summary, it appears that the most important function of MAG in the PNS is transmitting a signal from Schwann cells to axons that is needed for the stability of myelinated axons, whereas its principal function in the CNS is to transmit a signal in the reverse direction that promotes efficient myelination and oligodendrocyte vitality. 

The molecular and cellular events during Wallerian degeneration in the peripheral nervous system transform the damaged nerve into an environment that supports regeneration 518 Both Schwann cells and basal lamina are required for axonal regeneration... 

FIGURE BO-2 Wallerian degeneration in the PNS. After an axon is injured, resulting chromatolysis, i.e. stress reaction and increased protein synthesis, occurs in the neuronal cell body, with axonal and myelin degeneration distal to the injury. Growth-permissive Schwann cells secrete growth factors that stimulate axons to regenerate. 

Schwann cells are responsible for PNS trophic functions that, in CNS, are carried out by both oligodendroglia and astroglia. Schwann cell diseases usually present as disorders of myelination. Axonal degeneration and diminution in axonal diameter may also occur in primary disorders of Schwann cells, as a consequence of loss of Schwann cell trophic support for axons. (See also Chs 4 and 38.)... 

Stoll, G., Griffin, J. W., Li, C. Y. and Trapp, B. D. Wallerian degeneration in the peripheral nervous system participation of both Schwann cells and macrophages in myelin degradation./. Neurocytol. 18 671-683,1989. 

Incomplete nerve lesions provoke changes in the membrane excitability of afferents spared by the injury. These effects are the consequence of an altered cellular and signaling environment at the lesion site and in the DRG. Wallerian degeneration of axotomized nerve fibers involves degeneration and proliferation of Schwann cells, and an invasion of macrophages (discussed in Chs 30 and 36). Nerve injury is accompanied by a release of trophic... 

The neuron and the Schwann cell are the principal cell types in the PNS. There are great morphological, biochemical, and functional differences between neurons and Schwann cells, and this is reflected in the considerable variation in their vulnerability to toxic injury. Some toxic neuropathies are characterized primarily by injury of the neuron, its axon, or its terminal, as evidenced by the presence of axonal degeneration in peripheral nerve, while other toxic neuropathies are characterized primarily by Schwann cell injury, as evidenced by the presence of demyelination. Those neuropathies characterized by axonal injury are often categorized as axonal neuropathies, whereas those characterized by demyelination are categorized as demyelinating neuropathies. ... 

The vast majority of neurotoxic agents that affect the PNS preferentially cause axonal injury rather than Schwann cell injury. Axonal injury is usually manifested as axonal degeneration, a pathologic process characterized by complete dissolution of the axon. If the degeneration involves a myelinated axon, then the myelin sheath enveloping the degenerating axon also breaks down. This myelin breakdown, which occurs in the context of axonal degeneration, is not considered demyelination, since demyelination refers to loss of the myelin sheath from an intact axon. 

Thus, it is currently not clear how local factors in the target tissue modulate recovery from an immune attack in the PNS. As yet unknown genetic susceptibility factors may modulate the inflammatory process itself and the response of axons and of myelinating Schwann cells to the inflammatory assault. As an example, axonal degeneration occurring in autoimmune neuropathies clearly affects prognosis (Dalakas, 1999). Indeed, parallel expression of neurotrophic factors and their receptors in CIDP may reflect such survival mechanisms in the PNS (Yamamoto et al., 2002). 

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