Myelin intrusions in beaded nerve fibers

Small intrusions form in the internodes in or near the constrictions of beaded fibers prepared by fast-freezing and freeze-substituting mildly stretched nerves in the cat and rat. They appear as inwardly directed folds of the inner lamellae of the myelin sheath, or regularly formed spheres composed of lamellae with major dense and interperiod lines like those of the myelin sheath. A splitting of the lamellae and separation of the major dense lines may occur with an accumulation of Schwann cell cytoplasm between them, the result of an influx of cytoplasmic fluid from nearby constrictions. Longitudinally oriented microtubules have been observed in the intrusions, in the adaxonal Schwann cell cytoplasm, and in the innermost lamellae of the myelin sheath. The paranodes contain a number of larger intrusions in the form of spurs and globules along with shelve-like folds of the myelin sheath oriented in the longitudinal direction. Axoplasmic fluid driven from the constrictions during beading can enter the paranodes to smooth out their folds leaving the globular and spur-shaped myelin intrusions in isolation. Their wall thickness, measured from the central opening to the surface of the intrusion, is the same as that of the myelin sheath or, in some cases, double, the result of the folding of a spur-like intrusion upon itself. Intrusions unconnected to the sheath are seen in unbeaded fibers with regular, compact lamellae surrounded by axolemma. Others lack a covering axolemma and consist of variably disorganized and irregularly shaped lamellae suggesting that they are undergoing fragmentation and dissolution within the axon. The hypothesis is advanced that the intrusions in the internodes arise from an excess of lipid and other myelin components when the diameter of the sheath is reduced in the beading constrictions. In the paranodes, excess myelin components moved into these regions form the shelf-like folds which may fuse to form intrusions. These, separated from the myelin sheath, undergo fragmentation and dissolution and are carried by retrograde transport to the cell bodies where their constituent components can be reutilized.