Involvement of GDNF in Neuronal Protection against 6-OHDA-Induced Parkinsonism Following Intracerebral Transplantation of Fetal Kidney Tissues in Adult Rats

• Published in: Neurobiology of disease 2001-08, Vol.8 (4), p.636-646
• Main Authors: Borlongan, C.V., Zhou, F.C., Hayashi, T., Su, T.-P., Hoffer, B.J., Wang, Y.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Behavior, Animal; Corpus Striatum - metabolism; dopamine; Dopamine - metabolism; Enzyme-Linked Immunosorbent Assay; Fetal Tissue Transplantation; Glial Cell Line-Derived Neurotrophic Factor; Kidney - cytology; Kidney - metabolism; Kidney Transplantation; Male; motor asymmetry; Nerve Growth Factors; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - metabolism; neural transplantation; Neurons - cytology; Neurons - drug effects; Neurons - enzymology; Neuroprotective Agents - analysis; Neuroprotective Agents - metabolism; Oxidopamine; Parkinson's disease; Parkinsonian Disorders - pathology; Parkinsonian Disorders - surgery; Rats; Rats, Sprague-Dawley; striatum; substantia nigra; Substantia Nigra - cytology; Substantia Nigra - surgery; Sympatholytics; Transplants; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1006/nbdi.2001.0410

Exogenous application of transforming growth factors-β (TGFβ) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGFβ trophic factors, we transplanted these tissues directly into the substantia nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K+-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts. In contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K+-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors.