KIDNEY COGRAFTS ENHANCE FIBER OUTGROWTH FROM VENTRAL MESENCEPHALIC GRAFTS TO THE 6-OHDA-LESIONED STRIATUM, AND IMPROVE BEHAVIORAL RECOVERY

Recent studies have demonstrated the presence of many different neurot rophic factors in the developing and adult kidney. Due to its producti on of this mixture of neurotrophic factors, we wanted to investigate w hether fetal kidney tissue could be beneficial for neuritic fiber grow th and/or cell survival in intracranial transplants of fetal ventral m esencephalic tissue (VM). A retrograde lesion of nigral dopaminergic n eurons was performed in adult Fischer 344 male rats by injecting 6-hyd roxydopamine into the medial forebain, The animals were monitored for spontaneous locomotor activity in addition to apomorphine-induced rota tions once a week. Four weeks following the lesion, animals were anest hetized and embryonic day 14 VM tissue from rat fetuses was implanted stereotaxically into the dorsal striatum, One group of animals receive d a cograft of kidney tissue from the same embryos in the same needle track, The animals were then monitored behaviorally for an additional 4 months, There nas a significant improvement in both spontaneous loco motor activity (distance traveled) and apomorphine-induced rotations w ith both single VM grafts and VM-kidney cografts, with the VM-kidney d ouble grafts enhancing the motor behaviors to a significantly greater degree, Tyrosine hydroxylase (TH) immunohistochemistry and image analy sis revealed a significantly denser innervation of the host striatum f rom the VM-kidney cografts than from the single VM grafts, TH-positive neurons were also significantly larger in the cografts compared to th e single VM grafts, In addition to the dense TH-immunoreactive innerva tion, the kidney portion of cografts contained a rich cholinergic inne rvation, as evidenced from antibodies against choline acetyltransferas e (ChAT), The striatal cholinergic cell bodies surrounding the VM-kidn ey cografts were enlarged and had a slightly higher staining density f or ChAT, Taken together, these data support the hypothesis that neurot rophic factors secreted from fetal kidney grafts stimulated both TH-po sitive neurons in the VM cografts and cholinergic neurons in the host striatum, Thus, these factors may be combined for treatment of degener ative diseases involving both dopaminergic and cholinergic neurons. (C ) 1998 Elsevier Science Inc.