The clonal cell line, RN46A-B14, was isolated following transfection of the gene encoding rat brain-derived neurotrophic factor (BDNF) into RN46A cells. RN46A-B14 cells synthesize and secrete biologically active BDNF in vitro and synthesize serotonin (5-HT) following partial membrane depolarization. Two weeks following RN46A-B14 cell transplantation into the adult rat cortex and hippocampus, there is a threefold increase in survival of RN46A-B14 cells compared to RN46A cells. The grafted RN46A-B14 cells immunohistochemically stain for BDNF and 5-HT, while RN46A cells transfected with vector only are negative for both BDNF and 5HT. In addition, RN46A-B14 cells attain more morphologically complex phenotypes, indicating enhanced neuronal differentiation. Autocrine secretion of BDNF by RN46A-B14 cells thus potentiates survival and can be used to deliver both BDNF and 5-HT in vivo.
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