Co-transplantation of fetal lateral ganglionic eminence and ventral mesencephalon can augment function and development of intrastriatal transplants.
Methods to increase the development and sustained function of embryonic mesencephalic dopamine cells after transplantation into dopamine (DA)-depleted striatum are currently under investigation. Elements that are crucial for the maturation and connectivity of neurons during normal development of the brain may also play a role in the development and integration of grafted embryonic tissue. Based on in vitro and in vivo observations of the enhancing effects of striatal tissue on nigral dopaminergic cell development and survival, we demonstrate that inclusion of embryonic striatal cells, specifically from the lateral ganglionic eminence (LGE), produces dopaminergic transplants with augmented functional effects. Rats neonatally DA-depleted and co-transplanted with embryonic nigral and LGE cells developed improved functional outcome when compared with animals receiving only nigral cells, and they required the transplantation of fewer nigral cells to produce a strong behavioral effect. Anatomically, the inclusion of LGE cells produced increased DA cell survival, a higher density of reinnervation into the DA-depleted host striatum, and patches of DA fibers within the co-transplants. There were also an increased number of host striatal cells which induced the immediate-early gene c-fos in co-transplanted animals compared to animals receiving nigral cells alone, indicating a higher degree of host-cell activation. The ability to enhance function, cell survival, reinnervation, and host activation with nigral-striatal co-transplants in the presence of fewer nigral cells supports the hypothesis of a trophic influence of striatal cells on nigral DA cells.
Costantini
L C
LC
Wadsworth Center for Laboratories and Research, University at Albany School of Public Health, New York State Department of Health, 12201-0509, USA. Costantini@helix.mgh.harvard.edu
Snyder-Keller
A
A
D000661:Amphetamine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000637:transplantation*; D003714:Denervation; D004298:Dopamine / Q000032:analysis; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000637:transplantation*; D009434:Neural Pathways; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D016627:Oxidopamine; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology; D013565:Sympatholytics; D013566:Sympathomimetics
D016760:Proto-Oncogene Proteins c-fos; D013565:Sympatholytics; D013566:Sympathomimetics; D016627:Oxidopamine; D000661:Amphetamine; D004298:Dopamine