An ultrastructural study of oligodendrocytes in zitter rat: a new animal model for hypomyelination in the CNS

Abstract

The ultrastructural alterations in oligodendrocytes in the zitter rat--a newly established animal model of CNS hypomyelination--were studied in animals between 3 and 37 weeks of age. Throughout the observation period, the most characteristic alteration was the presence of abnormal structures associated with nuclear membranes and resembling split myelin lamellae. The structures consisted of stacks of membranes continuous with the inner and outer membranes of the nuclear envelope or with plasma membranes. This abnormality was prominent at 3 weeks of age, when initial myelination was probably still occurring. It was decreased transiently at 12 weeks of age and then again increased slightly with advancing age. However, the mean incidence of this abnormality was approximately 5% of the oligodendrocyte nuclei in randomly examined electron micrographs. As the small membranous abnormalities were observed in a few serial sections, the actual incidence is believed to be several times higher than 5%. Such membranous abnormalities were also detected in some mitochondria, in some cisternae of rough endoplasmic reticulum, and in some lysosomes, all at lower incidence rates. Some aberrant or elongated myelin sheath formations, an increased number of radial components and intracytoplasmic inclusions in oligodendrocytes were also observed. These findings suggest that functional abnormalities in membrane biosynthesis including the myelin sheaths and the nuclear membranes in oligodendrocytes are closely related to the hypomyelination in the CNS and may be related to the genetic abnormality in the zitter rat.