A myotrophic protein from the chicken sciatic nerve has been found to be similar if not identical to transferrin, the iron-binding and transport protein in the blood. The role of transferrin (Tf) in promoting muscle growth is becoming well documented, but other possible roles for transferrin particularly in the nervous system are relatively unexplored. Two recent reports indicate that Tf is utilized in the central nervous system: (i) Tf receptors are present in the rat brain and (ii) neurons in culture will take up iron, but the iron uptake is blocked in the presence of Tf inhibitors. This proposal is designed to localize, describe and examine the distribution of Tf-positive cells in the rat central and peripheral nervous system using rat transferrin antisera and the peroxidase anti-peroxidase method for immunohistochemistry. Our preliminary results have found that the oligodendrocytes in the central nervous system and Schwann cells of the peripheral nervous system label following immunoreaction with Tf antiserum. Thus our data suggest that the perineuronal satellite ologodendrocytes provide the neurons (and possible other glia) with the transferrin needed to takeup iron for normal function. No neuronal cells are Tf-positive in the adult, but anterior motor horn cells in the 20 day old rat pup are Tf-positive. Following the basic description studies, the response of Tf-positive cells and the Tf-like protein will be examined in a series of experimental studies: 1) callosal lesions in the cerebral cortex; 2) transection of the spinal cord; 3) nerve crush injury to the sciatic and optic nerves. The proposed studies will examine Tf production in a non-regenerating model after axotomy (callosal, spinal and optic nerve) and Tf production in a regenerating model (sciatic nerve). The Tf response of the perineuronal oligodendrocytes and associated neurons of the cerebral cortical and spinal gray matter will be examined to determine if there are alterations in their morphology or Tf response following a lesion. Because Tf-positive oligodendrocytes are present throughout the central nervous system, a more general effect of Tf other than its described myotrophic influence is evident. It is expected that the proposed experiments will result in data which will be relevant to a number of pathological conditions in which iron deficiency or accumulation or demyelination accompanies the disease state.
