Oligodendrocytes Schwann Cells and Myelination

The function of oligodendrocytes is to produce the myelin sheaths that insulate axons in the CNS. Myelinating Schwann cells serve the same function in the PNS, but there are also significant populations of nonmyelinating and perisynaptic (terminal) Schwann cells (Figure 8.1). Myelinating and nonmyelinating Schwann cells are equally numerous. These multiple Schwann cell types perform many of the diverse functions performed by astrocytes in the CNS - such as structure, metabolism, regulation of the microenvironment, and signalling. These functions are absolutely vital for PNS development, physiology and pathology. In contrast, oligodendrocytes can be defined by their exclusive function of myelination. There are 'nonmyelinating oligodendrocytes' in the CNS grey matter, but they are minor populations and their functions are unknown; it is even questioned that they are oligodendrocytes.

Myelinating Schwann cells or oligodendrocytes and the axons they support are interdependent functional units. The development of myelinating cells depends on a series of coordinated signals from axons. Similarly, the radial growth of axons (axon's diameter) and the myelin sheath (number of lamellae) are interdependent, resulting in the g-ratio of axons: number of myelin lamellae (1:10), which is a constant in the CNS and PNS. Furthermore, mature axons and myelinating cells continue to depend on each other for normal function and integrity: the loss of axons results in degeneration of oligodendrocytes and de-differentiation of Schwann cells; conversely, axons degenerate in the absence of appropriate support from Schwann cells and oligodendrocytes. The relationship between myelinating cells and axons is perhaps the clearest demonstration of the interdependence of neurones and glia.

Nonmyelinating Schwann cells surround bundles of small-diameter unmyelinated axons. These serve multiple functions, physically supporting and separating unmyelinated axons with fine processes, as well as providing physiological support in the form of ion homeostasis and preventing ephaptic transmission between axons. Mature nonmyelinating Schwann cells express a number of surface



Schwann cell

Schwann cell

Schwann Cell

Muscle endplate

Figure 8.1 Schwann cells. There are equal numbers of myelinating and nonmyelinating Schwann cells in the PNS. Myelinating Schwann cells myelinate a single axon, which has a critical diameter above 1 |xm. Nonmyelinating Schwann cells ensheath multiple unmyelinated axons, which are smaller than the critical diameter of 1 |xm. Perisynaptic (terminal) Schwann cells ensheath terminal axonal branches and synaptic boutons at the neuromuscular junction; their basal lamina fuses with that of the muscle fibre and motor endplate molecules characteristic of immature Schwann cells that are not found on mature myelinating Schwann cells, including the cell adhesion molecule L1 and neural cell adhesion molecule (NCAM). In addition, nonmyelinating Schwann cells can adopt a myelinating phenotype under experimental conditions.

Perisynaptic (terminal) Schwann cells at the neuromuscular junction (NMJ)

ensheath terminal axonal branches and synaptic boutons. They are covered by a basal lamina that fuses with that of the muscle fibre and motor endplate.

Perisynaptic Schwann cells play essential roles in synaptic function, maintenance, and development. In addition, they respond to nerve activity by increased intracellular Ca2+ and are capable of modulating synaptic function in response to pharmacological manipulations. During development they contribute to the maturation and extension of the motor endplate and they stabilize the NMJ. They also regulate the efficacy of synaptic transmission and neurotransmitter release by modulating perisynaptic ions and Ca2+ concentration, and may also induce postsynaptic acetyl-choline receptor aggregation. Furthermore, in regeneration perisynaptic Schwann cells guide the growth of regenerating presynaptic nerve terminals at adult NMJs.

Schwann cell basal lamina. A major difference between Schwann cells and oligodendrocytes is that Schwann cells form a basal lamina around their abax-onal cytoplasmic membranes. In longitudinal section, the basal lamina forms a continuous tube along the axon, bridging the nodal gap between Schwann cells. In contrast, oligodendrocytes and CNS myelin do not have a basal lamina, and myelin sheaths are directly apposed to each other within bundles or fascicles. The major constituents of the basal lamina are the extracellular matrix (ECM) components, laminin-2 (merosin), heparan sulphate proteoglycans (e.g. perlecan, agrin), collagen type IV, and fibronectin. The basal lamina is crucial for myelination, and its disruption results in severe dysmyelination, as for example in dystrophic mice which lack laminin-2. Schwann cells express a number of receptors for basal lamina components, including dystroglycan-dystrophin-related protein 2 (DRP2) and integrins (e.g. a6/pi), which are essential for myelination. In addition, many of the ECM components of the basal lamina promote axon growth and are therefore important during PNS regeneration.

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