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), 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 TGF beta 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.
Borlongan
C V
CV
Cellular Neurobiology Branch, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.
Zhou
F C
FC
Hayashi
T
T
Su
T P
TP
Hoffer
B J
BJ
Wang
Y
Y
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016332:Fetal Tissue Transplantation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000032:analysis / Q000378:metabolism*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000601:surgery; D013565:Sympatholytics; D019737:Transplants; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine