Host dopaminergic afferents affect the development of DARPP-32 immunoreactivity in transplanted embryonic striatal neurons.
Homotopic transplantation provides an interesting way to observe the relationships between developing cells and ingrowing host afferents. We have performed a complete and selective elimination of the mesostriatal dopaminergic system in adult rats to observe the influence of its absence on the development and chemical differentiation of embryonic striatal cells. Cell suspensions from striatal primordia of 14-15-day-old embryos were transplanted into host striata that were (i) neuron-depleted by kainic acid (control group) or (ii) deprived of dopamine by 6-hydroxydopamine prior to the neuronal depletion by kainic acid (experimental group). The expression of dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein (DARPP-32) by transplanted cells was observed in correlation with their innervation by host dopaminergic afferents which in turn were identified by tyrosine hydroxylase immunohistochemistry. Observations were made between four days and three months after transplantation. Four days after transplantation, no immunoreactivity for DARPP-32 was observed in transplants of control animals despite the presence of tyrosine hydroxylase-immunopositive fibers growing from the host to discrete cell clusters in the transplant. DARPP-32-labeled cells appeared soon afterwards. Six days after transplantation they displayed varying intensities of immunoreaction, ranging from just detectable to normal levels and were specifically targeted by developing tyrosine hydroxylase-immunopositive fibers. The number of DARPP-32-labeled cells increased rapidly and they formed increasingly compact clusters. Fourteen days after transplantation and afterwards, all the DARPP-32-labeled cells displayed an intensity of immunoreaction and a distribution comparable to that observed in long-term transplants. Transplants in the experimental hosts displayed the same organization and developmental features as the control transplants with the exception of DARPP-32 labeling which was not detected before eight days after transplantation. Ten days after transplantation, the distribution and intensity of DARPP-32 labeling was similar to that observed at six days in the control group. The evolution of DARPP-32 labeling after 10 days in the experimental group paralleled that observed six days post-transplantation and beyond in the control group. Dopaminergic mesostriatal host afferents are able to provide developing cells in grafted striatal tissues with normal innervation very rapidly. Despite this rapidity, the innervation does not seem to have any trophic influence on the general development of the transplant but does affect the onset time of the expression of neurochemical markers that are directly related to its synaptic function.(ABSTRACT TRUNCATED AT 400 WORDS)
INSERM CJF 91-02, U.F.R. de Médecine, Créteil, France.
B
B
Defontaines
M
M
Peschanski
B
B
Onteniente
D000344:Afferent Pathways / Q000166:cytology / Q000502:physiology*; D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D004298:Dopamine / Q000378:metabolism; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D016627:Oxidopamine / Q000494:pharmacology; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D007608:Kainic Acid; D004298:Dopamine