Somato-dendritic distribution of 5-HT1A and 5-HT1B autoreceptors in the BDNF- and cAMP-differentiated RN46A serotoninergic raphe cell line

The rapid differentiating effects of brain-derived neurotrophic factor (BDNF) or dibutyryl-cAMP (dBcAMP) were characterized on RN46A, a rat raphe-derived neuronal cell line [White, L.A., Eaton, M.J., Castro, M.C., Klose, K.J., Globus, M.Y., Shaw, G., Whittemore, S.R., 1994. Distinct regulatory pathways control neurofilament expression and neurotransmitter synthesis in immortalized serotonergic neurons. J. Neurosci. 14, 6744–6753]. After BDNF treatment, RN46A cells were serotonin-immunopositive and bipolar, and expressed the microtubule-associated-protein 2 (Map2). After dBcAMP treatment, the cells often became multipolar, bearing very long processes strongly immunopositive for serotonin and Map2.Under both conditions, the expression and distribution of 5-HT1A and 5-HT1B autoreceptors remained identical. 5-HT1A and Map2 immunolabelings were superimposable, as expected of their somato-dendritic targeting. Surprisingly, the distribution of 5-HT1B immunoreactivity was similar, in contrast with its usual localization in axons and nerve terminals in the brain. In conclusion, both BDNF and cAMP-differentiated RN46A cells towards a neuronal serotoninergic-like phenotype without the typical differential targeting of the 5-HT1 autoreceptors, an interesting model to study the molecular mechanisms ensuing the targeting of 5-HT1 autoreceptors to somas and dendrites.