Time-course and localization of transferrin receptor expression in the substantia nigra of 6-hydroxydopamine-induced Parkinsonian rats

Parkinson's disease is a neurodegenerative disease characterized by dopamin ergic cell death in the substantia nigra. The cause of the cell death is, h owever, obscure. Recently, accumulation of iron in the parkinsonian substan tia nigra and iron-catalysed free radical generation have been proposed as possible causes of nigral cell death. The transferrin receptor has been imp licated as a possible mediator of this iron accumulation in the parkinsonia n substantia nigra. The present study investigated the distribution of tran sferrin receptor-immunoreactive proteins and its co-localization with tyros ine hydroxylase in the normal rat substantia nigra and their expressions in the parkinsonian substantia nigra from three days to three months after 6- hydroxydopamine lesioning. Computer image analysis of the grey mean of tran sferrin receptor staining in the microvessels was also employed. The result s showed that the transferrin receptor immunolabelling was localized in som e neurons and glial cells in the normal substantia nigra pars compacta and pars reticulata, and that about 54% of tyrosine hydroxylase-positive cells were also stained with transferrin receptor. There was a decrease of tyrosi ne hydroxylase- and transferrin receptor-positive cells in the 6-hydroxydop amine-lesioned substantia nigra. The grey mean of transferrin receptor stai ning in microvessels in the lesioned substantia nigra was, however, not dif ferent from that in the control. It was concluded that transferrin receptors in neurons, glial cells and mic rovessels might not be responsible for iron accumulation in the parkinsonia n substantia nigra. The loss of transferrin receptor-immunopositive cells m ight, however, partly be accounted for by the death of transferrin receptor -positive dopaminergic cells induced by 6-hydroxydopamine lesioning. (C) 19 99 IBRO, Published by Elsevier Science Ltd.