Increase of transferrin receptors and iron uptake in regenerating motor neurons.

After injury, motor neurons exhibit a number of metabolic and protein changes that are assumed to be part of an inherent neuronal regeneration program, which, when activated, eventually leads to functional restitution. The mechanisms underlying this regeneration are unclear, but it may be expected that factors supporting neuronal growth or survival play an important role in the restoration of neuronal integrity. A number of neuronal growth-associated proteins have been identified, but their functional roles remain unclear. This paper shows that axotomy results in a strong increase in transferrin receptors (TfRs) in regenerating motor neurons and that this phenomenon is functionally associated with an elevated uptake of exogenous iron. The association of TfR expression in regenerating motor neurons with direct uptake of iron into the brain provides evidence that iron uptake into neural tissue may be related to neuronal metabolic activation. We suggest that the enhanced capacity of regenerating motor neurons to bind transferrin and to take up iron plays an important role in neuronal repair.