Myelin sheath

Stratum myelini

Also known as: myelin, medullary sheath

A segmented, multilayered, lipid-rich wrapping of glial membrane around axons. Oligodendrocytes form it in the CNS and Schwann cells in the PNS. It insulates the internodes so that action potentials jump between the nodes of Ranvier (saltatory conduction).

Neuron & Action Potential

Overview

Composition≈70–80% lipid, ≈20–30% protein

Internode length≈0.2–2 mm

Max conduction velocity≈120 m/s (vs 0.5–2 m/s unmyelinated)

Myelin forms when a glial process wraps an axon in many spiral turns (up to ≈100) of its own plasma membrane and extrudes the cytoplasm. The cytoplasmic surfaces fuse to form the major dense line, and the extracellular surfaces form the intraperiod line. The result is about 70–80% lipid, rich in cholesterol, galactocerebroside (galactosylceramide), sulfatide and sphingomyelin, and 20–30% protein. This high lipid content is why fibre tracts look white and why the white matter of the brain and cord is white.

Myelin is interrupted every 0.2–2 mm at the nodes of Ranvier, where voltage-gated Na⁺ channels are concentrated. Because the myelinated internode has a high membrane resistance and a low capacitance, current spreads passively and rapidly down the axon to the next node, which regenerates the action potential. This saltatory conduction raises velocity up to ≈120 m/s, compared with 0.5–2 m/s in unmyelinated fibres. It also saves energy, because ions cross the membrane only at nodes. Remnants of cytoplasm persist in PNS myelin as Schmidt–Lanterman incisures and at the paranodal loops.

Parts & subdivisions

CNS myelin (oligodendrocyte)
One oligodendrocyte myelinates internodes on up to ≈50 axons. No basal lamina or neurilemma. Main proteins PLP, MBP and MOG. Inhibits regeneration (Nogo-A, MAG). Target of multiple sclerosis.
PNS myelin (Schwann cell)
One Schwann cell forms one internode of one axon. It has a basal lamina and an outer nucleated neurilemma. Main proteins P0, PMP22 and MBP. Supports regeneration (bands of Büngner). Affected in Guillain–Barré syndrome and Charcot–Marie–Tooth disease.
Internode
The myelinated segment between two nodes, ≈0.2–2 mm long. Longer and thicker internodes conduct faster.
Node of Ranvier
The ≈1 µm unmyelinated gap where voltage-gated Na⁺ channels cluster at very high density and the action potential is regenerated.
Paranode and juxtaparanode
Glial loops anchored to the axon by septate-like junctions (Caspr, contactin, neurofascin-155) flank each node. The juxtaparanodes beyond them hold voltage-gated K⁺ channels, which are exposed and leak current when myelin is lost.
Schmidt–Lanterman incisures
Funnel-shaped channels of residual cytoplasm crossing the compact myelin, mainly in the PNS. They provide a transport route through the sheath.

Anatomy

Histology: Luxol fast blue (CNS) and osmium tetroxide stain myelin dark. On H&E it appears as clear spaces around axons, and in the PNS "herringbone" neurokeratin network may be seen. Electron microscopy shows periodic lamellae (≈12 nm) with alternating major dense and intraperiod lines.
Development: PNS myelination starts around the 4th fetal month. CNS myelination begins in the second trimester, proceeds caudal to rostral and posterior to anterior, and continues into the third decade, with the prefrontal cortex last. The corticospinal tract completes myelination by about 2 years, which explains the normal Babinski response in infants and the late acquisition of fine motor skills.

Function

Increases conduction velocity by up to ≈50-fold through saltatory conduction.
Reduces the metabolic cost of signalling, since Na⁺/K⁺-ATPase work is confined to the nodes.
Allows fast conduction in thin axons, saving space in the nervous system.
Provides metabolic support to axons and restricts axonal sprouting in the CNS.

Clinical significance

Multiple sclerosis (CNS demyelination)

Plaques of demyelination slow or block conduction. Classic features: optic neuritis, internuclear ophthalmoplegia (MLF), Lhermitte sign, and Uhthoff phenomenon, in which symptoms worsen with heat because conduction in partly demyelinated axons fails more easily as temperature rises. On visual evoked potentials, latency is prolonged.

Peripheral demyelination

In Guillain–Barré syndrome (acute), CIDP (chronic) and Charcot–Marie–Tooth 1, nerve conduction studies show markedly slowed velocities, conduction block and prolonged F waves. Contrast this with axonal neuropathies, where amplitude is reduced and velocity is relatively preserved.

Test yourself

Which cell forms myelin in the central nervous system?

Schwann cell
Astrocyte
Oligodendrocyte
Satellite cell

Answer: Oligodendrocyte

One oligodendrocyte myelinates internodes on many CNS axons (up to ≈50). A Schwann cell myelinates a single internode of one peripheral axon. This is why MS (oligodendrocytes, CNS) and GBS (Schwann cells, PNS) affect different parts of the nervous system.