Previous studies have indicated that neurotrophic factors, such as GDNF, protect against 6-hydroxydopamrne (6-OHDA) -induced lesions in rats. It has also been reported that GDNF mRNA is highly expressed in the fetal, but not adult kidney, suggesting that fetal kidney has GDNF -containing cells in vivo. In this study, we examined if grafting of fetal kidney cells lowers the toxicity induced by 6-OHDA. Fetal or adult kidney tissues (1 mm3), together with 9 mg 6-OHDA, were injected into right medial forebrain bundle of chloral hydrate-anesthetized Sprague-Dawley rats. One or three week post-surgery, animals was evaluated on the elevated body swing, amphetamine-induced rotation, and general locomotor activity tests. At both time periods, animals that received fetal, but not adult, kidney cells exhibited markedly reduced biased swing activity, fewer rotations, and increased general locomotor activity compared to those that received adult kidney cells. Immunostaining revealed that stronger TH activity was found in the striatum of animals receiving fetal, as compared to adult, kidney cell grafts. ELISA analysis indicates that fetal kidney contains high levels of GDNF protein. No GDNF was found in adult kidney tissue. Since fetal kidney may provide not only sustained GDNF release but also other neuroprotective trophic factors, such as OPI, neurturin, and TGF b, which synergistically interact with GDNF, the protection induced by fetal kidney transplantation may be more efficacious than exogeneous application of GDNF alone. In conclusion, our data indicate that fetal kidney grafts diminished 6-OHDA-induced toxicity, possibly through the release of neurotrophic factors. - Neuroprotection, Stroke, Trophic Factors
