Enhanced efficacy of nigral-striatal cotransplants in bilaterally dopamine-depleted rats: an anatomical and behavioral analysis.
When embryonic ventral mesencephalic tissue containing nigral dopamine (DA) neurons is transplanted into adult DA-depleted striatum, synaptic connections form and behavioral effects are observed. This study investigated the cotransplantation of embryonic striatal tissue as a means of enhancing the innervation, survival, and functional effects of nigral transplants. Rats neonatally DA-depleted, via bilateral intraventricular injections of 6-hydroxydopamine, developed turning in response to amphetamine and stress following unilateral transplantation of either nigral or combination nigral-striatal cell suspensions. Animals with cotransplants developed higher levels of turning to both stimuli and maintained these responses for a longer period of time post-transplantation, when compared with animals receiving transplants of nigral cells alone. In addition, these combination transplants required fewer dopaminergic cells to produce a strong behavioral effect on the host. Dense patches of tyrosine hydroxylase (TH)-immunoreactive fibers were observed within the cotransplants, yet no greater outgrowth of DA fibers into host striatum was detected. Amphetamine produced widespread induction of the immediate-early gene c-fos in cells of host striatum that extended beyond the transplant-derived DA innervation. After both amphetamine and stress, Fos protein was found within both types of transplants, but these Fos-immunoreactive cells did not colocalize with TH-immunoreactive cells nor dense TH-immunoreactive patches within the grafts. Thus, cotransplanted embryonic striatal tissue augments the effects of ventral mesencephalic transplants, possibly by providing a trophic influence that enhances the function of the DA cells without increasing cell survival.
Costantini
L C
LC
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany.
Vozza
B M
BM
Snyder-Keller
A M
AM
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism* / Q000502:physiology / Q000637:transplantation*; D004298:Dopamine / Q000172:deficiency*; D016332:Fetal Tissue Transplantation; D009068:Movement / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D016627:Oxidopamine; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D013312:Stress, Physiological / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry
D016760:Proto-Oncogene Proteins c-fos; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine