Neurotrophins differentially regulate the survival and morphological complexity of human CNS model neurons

To determine the effect of neurotrophins on the survival and morphological differentiation of CNS neurons, we examined NT2-N cells, which provide a un ique culture model for terminally differentiated and polar human neurons. H ere we report the development of conditions for the long-term culture of NT 2-N cells in low density and in chemically defined medium. We show that NT2 -N cells express mRNAs for TrkA, TrkB, and TrkC tyrosine kinase receptors a nd the low-affinity nerve growth factor receptor (p75NTR), All members of t he nerve growth factor-related family of neurotrophic factors promote neuro nal survival in long-term cultures with similar to 1 ng/ml for half-maximal survival. At high concentrations (>20 ng/ml), the neurotrophins reversed t he survival-promoting effect as judged by MTT [3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide] conversion. In contrast to the uniform ef fect of all neurotrophins on neuronal survival, brain-derived neurotrophic factor selectively induced an increased dendritic complexity. These results demonstrate that NT2-N cells provide a useful model to analyze the effect of neurotrophins on the survival and morphological differentiation of CNS n eurons in vitro. In addition, the data indicate that neuronal survival and the development of morphological complexity are differentially regulated in a multireceptor context.