Intrastriatal grafting of dopamine-containing neuronal cell suspensions: effects of mixing with target or non-target cells.

The effects of target and non-target cells on the growth and function of intrastriatal grafts of mesencephalic dopamine neurons have been studied in rats with unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway. Cell suspensions of ventral mesencephalon from 14-15-day-old rat fetuses (rich in developing dopamine neurons) were either grafted alone or grafted after mixing with equivalent numbers of cells obtained from the striatum (a major dopamine target area) or spinal cord (a non-target area for the mesencephalic dopamine neurons). The combined mesencephalic and striatal grafts gave rise to a greater area of dense innervation in the host caudate-putamen than grafts of mesencephalic cells alone or grafts of mesencephalic cells mixed with spinal cord cells. The number of surviving catecholamine-containing neurons did not differ significantly in the different types of grafts. In addition, there was an altered outgrowth pattern in the combined mesencephalic-striatal grafts consisting of small round islands of intensely fluorescent catecholamine-containing fibres, often in close association with the grafted dopamine neurons. In a subsequent biochemical study it was found that combined mesencephalic-striatal grafts exhibited dopamine levels and turnover that did not differ from grafts containing mesencephalic cells only. The mesencephalic-striatal cografts showed a trend toward enhanced behavioural effect, in terms of greater reduction in amphetamine-induced rotation asymmetry, when compared to other graft groups. It is suggested that the addition of embryonic striatal target cells can exert stimulatory effects on morphological development, and possibly functional parameters, of fetal dopamine cells also in vivo after intrastriatal grafting.(ABSTRACT TRUNCATED AT 250 WORDS)