Time course of dopaminergic cell death and changes in iron, ferritin and transferrin levels in the rat substantia nigra after 6-hydroxydopamine (6-OHDA) lesioning

Parkinson's disease is characterized by dopaminergic cell death in the subs tantia nigra. The underlying mechanism is, however, unknown. Though there a re increasing lines of evidence showing iron accumulation in the Parkinsoni an substantia nigra, it still remains obscure whether increased iron is the primary cause of dopaminergic cell death, or just a consequence of the pat hological process. It is also unclear how iron gains access to the Parkinso nian SN. To gain more understanding in these areas, the present study inves tigated the time course of dopaminergic cell death and of changes in the le vel of iron, ferritin and transferrin. The results showed that iron was inc reased after the significant nigral dopaminergic cell death induced by 6-hy droxydopamine injection into the rat substantia nigra. On the other hand, t he expression of transferrin was decreased. However, there was a temporal i ncrease in the number of ferritin positive microglia. The results indicated that iron increase was not the primary cause of dopaminergic cell death in the Parkinsonian rat. It was most likely the result of an accumulation of iron-laden microglia.