Effects of osmolality on PLP-null myelin structure: implications re axon damage.

In order to test the adhesiveness of PLP-null compact myelin lamellae we soaked aldehyde-fixed CNS specimens from PLP-null and control mice overnight in distilled water, in Ringer's solution or in Ringer's solution with added 1 M sucrose. Subsequent examination of the tissue by EM showed that both PLP-null and control white matter soaked in Ringer remained largely compact. After the distilled water soak, control myelin was virtually unchanged, but PLP-null myelin showed some decompaction, i.e., separation of myelin lamellae from one another. After the sucrose/Ringer soak, normal myelin developed foci of decompaction, but the great majority of lamellae remained compact. In the PLP-null specimens, in contrast, many of the myelin sheaths became almost completely decompacted. Such sheaths became thicker overall and were comprised of lamellae widely separated from one another by irregular spaces. Thus, in normal animals, fixed CNS myelin lamellae are firmly adherent and resist separation; PLP-null myelin lamellae, in contrast, are poorly adherent and more readily separated. Mechanisms by which impaired adhesiveness of PLP-null myelin lamellae and fluctuations in osmolality in vivo might underlie slowing of conduction and axon damage are discussed.