Peripheral nerve-dopamine neuron co-grafts in MPTP-treated monkeys: augmentation of tyrosine hydroxylase-positive fiber staining and dopamine content in host systems.
Previous studies of rats in our laboratory indicate that a molecule or molecules released by Schwann cells exert survival and growth-promoting effects on mesencephalic dopamine neurons. In the present study, we have begun to investigate the potential for Schwann cell augmentation of host dopamine fiber systems and embryonic dopamine neuron grafts in non-human primates. Ten adult male St Kitts African Green monkeys treated with the dopaminergic neurotoxin 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine one year previously, but behaviorally asymptomatic, served as hosts for implant studies. A segment of young adult monkey saphenous nerve was collected to serve as an implanted tissue source of Schwann cell-derived growth factors. Nerve was enclosed in a hollow semi-permeable polymer fiber for implantation into the lateral ventricle, with embryonic ventral mesencephalic tissue co-grafts containing developing dopamine neurons aimed at nearby locations in the caudate nucleus. Control implants consisted of an empty polymer fiber co-grafted with embryonic ventral mesencephalon. Our morphological observations indicate that while no clear augmentation of the morphology of grafted dopamine neurons attributable to co-grafted nerve was observed, this lack of influence may be related to the spatial separation of the co-grafted tissues. In contrast, some monkeys with nerve segments in the lateral ventricle exhibited increased tyrosine hydroxylase-positive fiber staining in the immediately adjacent lateral septal area and the ventricular wall of the caudate nucleus. This enhancement was not associated with empty polymer implants. Levels of dopamine and its metabolite homovanillic acid derived from tissue punches in the caudate nucleus and septal area support the view that monkeys exhibiting morphological enhancement of host dopamine systems also show biochemical increases in dopamine levels and changes in the direction of normalization of the homovanillic acid/dopamine ratio. Biochemical values from a single septal area tissue punch in one animal were an exception to this rule. This study suggests that while the utility of peripheral nerve as a source of dopamine graft augmentation in non-human primates remains to be demonstrated, grafted nerve has a stimulatory effect on host brain dopamine systems in adult, dopamine-depleted monkeys, and that this morphological effect can be dissociated from previously hypothesized injury-induced regeneration.
Collier
T J
TJ
Department of Neurobiology and Anatomy, University of Rochester School of Medicine, NY 14642.
Elsworth
J D
JD
Taylor
J R
JR
Sladek
J R
JR
Roth
R H
RH
Redmond
D E
DE
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002522:Chlorocebus aethiops; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D016332:Fetal Tissue Transplantation; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects / Q000201:enzymology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000637:transplantation*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000601:surgery*; D010525:Peripheral Nerves / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D012583:Schwann Cells / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid