Fos expression in intrastriatal striatal grafts: regulation by host dopaminergic afferents.
Previous studies have shown that transplants of fetal striatum, implanted into the ibotenic acid-lesioned striatum of adult rats, become innervated from the host nigrostriatal dopamine (DA) pathway. In the present study we have used DA-receptor-mediated expression of the Fos protein (i.e. the product of the immediate-early c-fos gene) as a cellular marker for functional dopaminergic host-graft interactions in the striatal grafts. Amphetamine (5 mg/kg; 2 h) induced Fos-like immunoreactivity in clusters of cells located mainly within the DARPP-32-positive areas within the transplants, i.e. within the striatum-like graft compartment which is preferentially innervated by the host DA afferents. As in the normal striatum, this effect was largely, although not completely, abolished by a 6-hydroxydopamine lesion of the ipsilateral nigrostriatal DA pathway. Apomorphine (0.25 mg/kg; 2 h) had no detectable effect in grafts with an intact host DA system. Two to 3 weeks after a 6-OHDA lesion of the host DA pathway (i.e. a time sufficient for DA receptor supersensitivity to develop), apomorphine-induced extensive Fos-activation selectively within the DARPP-32-positive areas of the graft. The magnitude of the response was similar to that seen in the DA-denervated host striatum. Dual Fos/DARPP-32 immunostaining revealed that the activated graft neurons were, at least in part, DARPP-32-positive. In intrastriatal grafts of fetal neocortical tissue, which were studied for comparison, the amphetamine- and apomorphine-induced effects on Fos expression were much smaller and similar to that seen in the DARPP-32-negative, non-striatal compartment within the striatal grafts.(ABSTRACT TRUNCATED AT 250 WORDS)
Mandel
R J
RJ
Department of Medical Cell Research, University of Lund, Sweden.
Wictorin
K
K
Cenci
M A
MA
Björklund
A
A
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D016380:Brain Tissue Transplantation / Q000502:physiology*; D003342:Corpus Striatum / Q000473:pathology / Q000502:physiology* / Q000637:transplantation*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology; D016762:Genes, fos; D007051:Ibotenic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D010750:Phosphoproteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000502:physiology*
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016760:Proto-Oncogene Proteins c-fos; D007051:Ibotenic Acid; D016627:Oxidopamine; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine