Transplantation of mesencephalic cell suspensions from wild-type and heterozygous Weaver mice into the denervated striatum: assessing the role of graft-derived dopaminergic dendrites in the recovery of function.
The Weaver (wv) mutation leads to a loss of mesencephalic dopamine cells and nigrostriatal dopamine axons in homozygosity (wv/wv) and to a deficiency of nigral dopaminergic dendrites without a concomitant loss of dopamine cell somata or axons in heterozygosity (wv/+). Previous studies have shown that grafts of foetal dopamine cells from wild-type (+/+) donors can survive when implanted into the wv/wv striatum, supply both an axonal and a dendritic innervation to the host, establish synaptic connections with host striatal neurons, and bring about a functional recovery evidenced by rotational asymmetry tests. The aims of the present study were to examine whether wv/+ dopamine cells maintain a "dendrite-poor" phenotype after transplantation to the denervated striatum, and to compare their functional effects with those of wild-type (+/+) grafts in reversing amphetamine-induced turning behaviour. To that end, +/+ and wv/+ ventral mesencephalic tissue (dissected out from E10-E12 foetal mice and made into a cell suspension by enzymatic and mechanical dissociation) was stereotactically grafted into the right striatum of either wv/wv hosts or +/+ hosts subjected in advance to 6-OHDA lesions of the right substantia nigra. Viability and morphology of grafted neurons were assessed by tyrosine hydroxylase immunocytochemistry on serial sections of the host forebrains. Dopamine cell bodies survived in comparable numbers in the grafts regardless of donor genotype; however, grafts of either genotype contained fewer dopaminergic cells when they were hosted in the wv/wv striatum as compared to the striatum of +/+ mice with 6-OHDA lesions. Despite the survival of cell somata, the dendritic arborisation of wv/+ cells was strikingly poorer than that of +/+ cells in grafts placed into both host types, most likely reflecting their in situ phenotypic abnormality. Recipient wv/wv mice with +/+ and wv/+ grafts exhibited 88% and 83% left rotations, respectively; 6-OHDA hosts with +/+ and wv/+ grafts showed 178% and 165% reversals of asymmetry, respectively. The differences between the effects of +/+ and wv/+ grafts were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)
Witt
T C
TC
Department of Surgery, Indiana University School of Medicine, Indianapolis 46202, USA.
Triarhou
L C
LC
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000502:physiology*; D003712:Dendrites / Q000502:physiology*; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006651:Histocytochemistry; D008636:Mesencephalon / Q000637:transplantation*; D051379:Mice; D008817:Mice, Mutant Strains / Q000196:embryology; D011247:Pregnancy
D004298:Dopamine