IRON PROTEINS AND OLIGODENDROCYTIC FUNCTION

Project: Research project

Project Details

Description

The long term goal of this research project is to understand iron
regulation in the nervous system. Many neuropathological conditions are
thought to involve disruptions in iron metabolism including Parkinson's and
Alzheimer's disease, but relatively little knowledge exists concerning iron
metabolism in the brain. This proposal focuses on the three major proteins
in iron metabolism; transferrin (Tf; iron mobilization), the transferrin
receptor, and ferritin (iron storage). Recently, Tf, and the mRNA for Tf,
iron and ferritin have all been demonstrated either specifically or
predominantly in oligodendrocytes. The long established function of
oligodendrocytes as myelin producing cells actually only accounts for the
function of 1/3 of their population. Perivascular and perineuronal
oligodendrocytes exist in gray matter (which contain the major iron
components) whose function under normal conditions is not established.
These gray matter and a subset of white matter oligodendrocytes may be iron
regulatory cells. The independence of the expression of the three major
iron proteins and iron accumulation to myelination will be demonstrated
using a chronic)quaking) and a reversible (female carrier of the jimpy
gene) hypomyelinating murine mutants. The levels of iron proteins should
reach a plateau in both the animal models, but will undergo a second
increase in the reversible hypomyelinating model in association with
increased metabolis demands of myelination. Immunohistochemistry,
quantitative assay, receptor binding and molecular approaches will be used;
the latter technique will yield information regarding whether control of
iron protein synthesis is at the transcriptional or translational leve.
Tissue culture studies will determine if iron and Tf in culture medium
effect the synthesis of ferritin, the Tf receptor and Tf by normal and
"jimpy" oligodendrocytes. Also the mechanism of iron uptake by
oligodendrocytes will be determined. Finally, we will compare accumulation
of iron components in Schwann cells in tissue culture under myelinating and
non-myelinating conditions. The significance of this proposal is that it
addresses two area of neurobiology about which little is known: iron
regulation in the nervous system and oligodendrocytic/Schwann cell
physiology and is thus relevant to neurodegenerative disorders and
dysmyelinating diseases.
StatusFinished
Effective start/end date12/31/896/30/01

Funding

  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke
  • National Institute of Neurological Disorders and Stroke

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