THE NEUROTROPHINS BDNF, NT-3 AND NT-4 5, BUT NOT NGF, UP-REGULATE THECHOLINERGIC PHENOTYPE OF DEVELOPING MOTOR-NEURONS/

Although developing motor neurons express low-affinity nerve growth fa ctor (NGF) receptors, there is no known biological effect of NGF on de veloping or adult motor neurons. In this study, we found that, unlike NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) a nd neurotrophin-4/5 (NT-4/5) stimulated cholinergic phenotype by incre asing choline acetyltransferase (CAT) activity in cultures enriched wi th embryonic rat motor neurons. Ciliary neurotrophic factor (CNTF) als o stimulated CAT activity. The effects of BDNF and NT-4/5 on CAT activ ity appeared to be synergistic with that of CNTF. Cotreatment with BDN F and NT-3 resulted in an additive effect, suggesting that signal tran sduction was mediated through different high-affinity receptors tyrosi ne kinases B and C (Trk B and Trk C). However, cotreatment with BDNF a nd NT-4/5 did not result in an increase in CAT activity greater than t hat of either BDNF or NT-4/5 alone, suggesting that their effects were mediated via the same receptor Trk B. Supporting our findings that sp inal cholinergic neurons are responsive to trophic actions of members of the neurotrophin family, motor neuron-enriched cultures were found to express mRNA for Trk B and Trk C, which have been identified as hig h-affinity receptors for BDNF and NT-4/5, and NT-3, respectively.