Adaption of the serotoninergic neuronal phenotype in the absence of 5-HT autoreceptors or the 5-HT transporter: involvement of BDNF and cAMP

• Published in: The European journal of neuroscience 2004-02, Vol.19 (4), p.937-944
• Main Authors: Rumajogee, Prakasham, Vergé, Daniel, Hanoun, Naïma, Brisorgueil, Marie-Jeanne, Hen, René, Lesch, Klaus-Peter, Hamon, Michel, Miquel, Marie-Christine
• Format: Article
• Language: English
• Subjects: 5-HT autoreceptors; 5-HT phenotype; 5-HT transporter; Adaptation, Physiological - drug effects; Adaptation, Physiological - physiology; Animals; Autoreceptors - deficiency; Autoreceptors - genetics; BDNF; Brain-Derived Neurotrophic Factor - pharmacology; Brain-Derived Neurotrophic Factor - physiology; cAMP; Carrier Proteins - genetics; Cognitive Sciences; Cyclic AMP - pharmacology; Cyclic AMP - physiology; Female; Life Sciences; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Membrane Transport Proteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Neurons - drug effects; Neurons - metabolism; Neurons and Cognition; Phenotype; Pregnancy; Receptors, Serotonin - deficiency; Receptors, Serotonin - genetics; Serotonin Plasma Membrane Transport Proteins
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/j.0953-816X.2004.03194.x

Serotonin 5‐HT1A and 5‐HT1B receptors and the 5‐HT transporter are key regulators of the serotoninergic neuronal phenotype. We show here that genetic deletion of any of these elements differentially regulates 5‐HT neuronal number in rostral raphe cultures from E14 mice. Serotonin neuronal number was increased by almost four‐fold and 1.8‐fold in cultures from 5‐HT1AR−/− and 5‐HT1BR−/− mice, respectively. In contrast, the lack of serotonin transporter expression was associated with a 50% decrease in 5‐HT neuronal number. In raphe cultures from the rat, BDNF and cAMP have been shown to up‐regulate the neuronal serotoninergic phenotype through TrkB‐dependent mechanisms [Rumajogee et al. (2002) J. Neurochem., 83, 1525–1528]. Similar tyrosine kinase‐dependent up‐regulating effects, in the absence of serotoninergic key‐elements are reported here, on both 5‐HT neuronal number and neurites length. However, the extents of BDNF‐triggered and cAMP‐triggered effects on serotoninergic neuritic length were approximately 1.5‐fold higher in 5‐HT1AR−/− mutants. These findings show that the up‐regulatory mechanisms triggered by BDNF on serotoninergic neuronal number and neurite extension are different and that the latter are partially linked to 5‐HT, probably through 5‐HT1A autoreceptors. Together, these data suggest that serotonin autoreceptors, mainly 5‐HT1A but also 5‐HT1B, may be responsible for a tonic auto‐inhibitory effect of 5‐HT itself on the serotoninergic neuronal phenotype during embryonic development, particularly marked in the absence of the 5‐HT transporter.