Article date: 1992/6/26
PubMed ID: 1504828
Journal name: Brain research (ISSN: 0006-8993)
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)
Author List: Mandel R J, Wictorin K, Cenci M A, Björklund A
Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Dopamine and cAMP-Regulated Phosphoprotein 32; Nerve Tissue Proteins; Phosphoproteins; Proto-Oncogene Proteins c-fos; Ibotenic Acid; Oxidopamine; Apomorphine; Dextroamphetamine; Dopamine;
Mesh terms: Afferent Pathways/drug effects; Animals; Apomorphine/pharmacology; Brain Tissue Transplantation/physiology; Corpus Striatum/pathology; Dextroamphetamine/pharmacology; Dopamine/physiology; Dopamine and cAMP-Regulated Phosphoprotein 32; Female; Fetal Tissue Transplantation/physiology; Genes, fos; Ibotenic Acid/toxicity; Immunohistochemistry; Nerve Tissue Proteins/analysis; Oxidopamine/toxicity; Phosphoproteins/metabolism; Proto-Oncogene Proteins c-fos/analysis; Rats; Rats, Inbred Strains; Substantia Nigra/physiology;