Transferrin receptor expression in myelin deficient (md) rats.
The question of iron regulation in the brain is the subject of increasing interest as the evidence continues to accumulate that a loss of brain iron homeostasis plays a significant role in some neurodegenerative diseases. Most cells acquire iron through a specific receptor mediated process involving transferrin, the iron mobilization protein. It appears that in the brain, endothelial cells, neurons, and oligodendrocytes express the transferrin receptor. This study uses a strain of rats (myelin deficient, md) in which oligodendrocytes fail to mature, and examines the consequences of this genetic defect on the expression of the transferrin receptor in the brain. The affinity of transferrin for its receptor is similar between the cerebral cortex and cerebellum in both the normal and myelin deficient rats (Kd = 7.8-10.6 nM). The transferrin receptor density is normally 2-3 times higher in the cerebellum than in the cerebral cortex. In the myelin deficient rat strain, the density of the transferrin receptor is decreased in both the cerebrum (56%) and cerebellum (70%) compared to the littermate control animals. Because oligodendrocytes are the only cell type affected in this mutant, the results suggest that these cells are responsible for a considerable amount of the transferrin receptors that are expressed in the brain (excluding the endothelial cell contributions). These observations are consistent with the existing literature stating that oligodendrocytes are responsible for the majority of transferrin and transferrin mRNA which is expressed in the brain, and support the working hypothesis that imbalances in brain iron homeostasis, particularly during development, are associated with myelin disorders.
Roskams
A J
AJ
Department of Neuroscience and Anatomy, Pennsylvania State University, M.S. Hershey Medical Center 17033.
Connor
J R
JR
D000818:Animals; D001921:Brain / Q000648:ultrastructure; D002531:Cerebellum / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism; D012343:RNA, Transfer / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011990:Receptors, Transferrin / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D011990:Receptors, Transferrin; D012343:RNA, Transfer