BDNF and NT4/5 promote survival and neurite outgrowth of pontocerebellar mossy fiber neurons

The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic fac tor (BDNF), neurotrophin-3 (NT3), and NT4/5 are all found in the developing cerebellum. Granule cells, the major target neurons of mossy fibers, expre ss BDNF during mossy fiber synaptogenesis, To determine whether neurotrophi ns contribute to the development of cerebellar afferent axons, we character ized the effects of neurotrophins on the growth of mossy fiber neurons from mice and rats in vitro. For a mossy fiber source, we used the basilar pont ine nuclei (BPN), the major source of cerebellar mossy fibers in mammals. B DNF and NT4/5 increased BPN neuron survival, neurite outgrowth, growth cone size, and elongation rate, while neither NT3 nor NGF increased survival or outgrowth. In addition, BDNF and NT4/5 reduced the size of neurite bundles . Consistent with these effects, in situ hybridization on cultured basilar pontine neurons revealed the presence of mRNA encoding the TrkB receptor wh ich binds both BDNF and NT4/5 with high affinity. We detected little or no message encoding the TrkC receptor which preferentially binds NT3. BDNF and NT4/5 also increased TrkB mRNA levels in BPN neurons. In addition to previ ously established functions as an autocrine/paracrine trophic factor for gr anule cells, the present results indicate that cerebellar BDNF may also act as a target-derived trophic factor for basilar pontine mossy fibers. (C) 1 999 John Wiley & Sons, Inc.