A comparison of the effects of glial cell line-derived neurotrophic factor on spinal cord and cortex cerebri grafts.

Glial cell line-derived neurotrophic factor (GDNF) has trophic effects on developing dopamine neurons, enhances survival of embryonic motoneurons in vitro and prevents axotomy-induced motoneuron atrophy in vivo. Here we investigate effects of GDNF on grafts of cortex cerebri tissue from E18, P1 and P8 donors and on spinal cord tissue for P8 and adult animals transplanted to the anterior chamber of the eye of host rats. Grafts were treated with GDNF or cytochrome C on days 0, 5, 10, 15, 20 and 25 (total amounts 0.5 microgram GDNF/eye/injection). Spinal cord grafts from P8 donors treated with GDNF grew to sizes larger than controls, had higher numbers of neuron-like cells and showed increased areas of neurofilament immunoreactivity and decreased glial fibrillary acidic protein immunoreactivity. In contrast to the P8 spinal cord grafts, there were no such effects observed in adult spinal cord grafts or in E18, P1 or P8 cerebral cortex grafts. To determine if an endogenous source of GDNF might exert similar effects on spinal cord grafts, we transplanted spinal cord tissue from P1 together with pieces of developing kidney, known to express high levels of GDNF mRNA. Spinal cord cografted with kidney tissue grew to a slightly larger extent then controls. We conclude that GDNF exerts a powerful trophic effect on P8 spinal cord grafts, although GDNF appears unable to support survival of grafted adult spinal cord tissue. Grafts of cortex cerebri from several different stages of development were not affected.