Morphological and behavioral drawbacks of fetal dopaminergic grafts, prelabeled with Phaseolus vulgaris leucoagglutinin.
The anterograde tracer Phaseolus vulgaris Leucoagglutinin (Pha-L) was tested as a fetal cell marker in short-term labeling of a fetal dopaminergic cell suspension and in long-term surviving grafts in vivo. As a model we used the grafting of fetal dopaminergic cells into the denervated caudate putamen of the rat. Short-term labeling revealed that the viability of the fetal cells was not affected by the Pha-L incubation within the 4 h of the test period. Yet, a subtle difference was noticed in the morphological development of the fetal neurons. Whereas many dopaminergic cells in the control suspension developed from an initially round soma to a more triangular or bipolar one, Pha-L-incubated cells maintained their round appearance. Moreover, cells with developing neurites were commonly noted in the control suspension, but were absent after incubation with Pha-L. Long-term effects of Pha-L were studied in three groups of unilaterally 6-hydroxydopamine-lesioned rats, which all received an injection of a fetal dopaminergic cell suspension in the denervated caudate putamen. The first group (T-Pha-L) received dopaminergic cells, prelabeled with Pha-L. The second group (T-saline) received cells incubated with vehicle (saline). The third group (T) received only dissociated cells. Eight weeks after the implantation the morphological analysis showed a minor Pha-L-immunoreactivity inside the labeled grafts. We detected Pha-L-positive fiber particles as well as weakly Pha-L-positive spots, presumably cell bodies. Pha-L-labeled grafts were significantly decreased in graft volume and contained markedly less dopamine-immunoreactive (DAi) cells than the control grafts of groups T-saline and T. The ratio DAi cell type I (cell with < or = 3 processes)/DAi cell type II (cell with > or = 4 processes) was approximately 8 in the control groups and 3 in group T-Pha-L. This suggests primarily a toxic effect of Pha-L and DAi cell type I neurons. Our behavioral data revealed that the Pha-L-labeled grafts did not cause a recovery from lesion-induced motor asymmetries.(ABSTRACT TRUNCATED AT 400 WORDS)
Dolleman-Van der Weel
M J
MJ
Research Institute Neurosciences Vrije Universiteit, Faculty of Medicine, Department of Pharmacology, Amsterdam, The Netherlands.
Nijssen
A
A
Steinbusch
H W
HW
D000818:Animals; D001058:Apomorphine; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism*; D016332:Fetal Tissue Transplantation; D008297:Male; D010835:Phytohemagglutinins / Q000009:adverse effects* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects
D010835:Phytohemagglutinins; C100156:leukoagglutinins, plants; D001058:Apomorphine; D004298:Dopamine