Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats

Exogenous application of transforming growth factors-beta (TGF beta) family proteins, including glial cell line-derived neurotrophic factor (GDNF), ne urturin, activin, and bone morphogenetic proteins, has been shown to protec t neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effe cts for treatment of neurodegenerative diseases. Because fetal kidneys expr ess many TGF beta trophic factors, we transplanted these tissues directly i nto the substantial nigra after a unilateral 6-hydroxydopamine lesion. We f ound that animals that received fetal kidney tissue grafts exhibited (1) si gnificantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near nor mal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatu m, (3) a preservation of K+-induced dopamine release in the lesioned striat um, and (4) high levels of GDNF protein within the grafts. In contrast, les ioned animals that received grafts of adult kidney tissues displayed signif icant behavioral deficits, dopaminergic depletion, reduced K+-mediated stri atal dopamine release, and low levels of GDNF protein within the grafts. Th e present study suggests that fetal kidney tissue grafts can protect the ni grostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotro phic factors. (C) 2001 Academic Press.