SYNERGISTIC BUT TRANSIENT RESCUE EFFECTS OF BDNF AND GDNF ON AXOTOMIZED NEONATAL MOTONEURONS

Brain-derived neurotrophic factor (BDNF) and glial cell line-derived n eurotrophic factor (GDNF), members of distinct families of polypeptide growth factors, have been shown to support motoneurons under various in vitro and in vivo conditions. We used a model of motoneuron cell de ath induced by sciatic nerve section in newborn rats and compared the efficacy of BDNF and GDNF administered alone or simultaneously in orde r to determine whether combinations of neurotrophic proteins can produ ce more potent motoneuron rescue than individual factors. The factors were administered by different methods, including (i) a single dose on to the transected nerve, (ii) continuous delivery from implanted slow -release polymer rods (BDNF) or encapsulated cells (GDNF), and (iii) r epeated systemic injections (BDNF). Irrespective of the method of admi nistration, either factor alone produced rescue effects which dramatic ally declined at two weeks as compared to one week post-lesion. In con trast, this decrease was significantly reduced when BDNF and GDNF were used simultaneously provided that one factor was applied on to the ne rve while the other was continuously released from the rods or capsule s. Other combinations in which GDNF was replaced by ciliary neurotroph ic factor or axokine-1 failed to reproduce such additive activity.Two conclusions can be made from these experiments. First, when BDNF and G DNF are administered simultaneously but by distinct routes of delivery , their survival-promoting effects on the injured developing motoneuro ns are potentiated; second, even continuous delivery of each of these trophic factors alone cannot completely abrogate the time-dependent de cline in rescue effects in this model of motoneuron cell death. (C) 19 98 IBRO. Published by Elsevier Science Ltd.