The development of the transferrin-transferrin receptor system in relation to astrocytes, MBP and galactocerebroside in normal and myelin-deficient rat optic nerves.

The factor(s) which control the onset of myelination are unknown. It is now accepted that transferrin (Tf), the major iron transport protein in vertebrates, is found in oligodendrocytes in the adult brain. Because of the importance of iron in basic cell metabolism we have hypothesized that iron (mobilized by Tf) may be a permissive agent in the process of myelination. The present study was designed to determine with immunohistochemistry the relationship of Tf receptor expression, Tf accumulation, and the expression of myelin components myelin basic protein (MBP) and galactocerebroside (GAlC)) in the developing rat optic nerve. In addition to Tf and its receptor, the developmental pattern for GalC reported in this study has not been examined in the rat optic nerve. Furthermore, a myelin mutant strain of rats was used to determine if a lack of myelin production affects the Tf-Tf receptor system. Our study found that Tf receptor was expressed from birth on blood vessels and was first seen in the parenchyma of the nerve at 8 days of age. The expression of the Tf receptor preceded that of Tf, MBP or GalC. The accumulation of Tf by oligodendrocytes occurred about the same time as the intracellular appearance of MBP and GalC which was shortly after the onset of myelination. Tf-positive cells as well as MBP- and GalC-positive cells increased in number and staining intensity with age whereas the expression of the Tf receptor declined after reaching a peak at 15 days of age. In the optic nerves of myelin-deficient rats, the Tf receptor expression and Tf accumulation was confined to the vasculature. The results of this study suggest that the expression of the Tf receptor is an early event in oligodendrocytic maturation and is followed by the intracellular accumulation of myelin components and Tf. The temporal association of Tf and myelin production suggests that further study is warranted regarding the possibility that the Tf-iron system supports or perhaps even permits the initiation of the process of myelination.