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Adaption of the serotoninergic neuronal phenotype in the absence of 5‐HT autoreceptors or the 5‐HT transporter: involvement of BDNF and cAMP
Author(s) -
Rumajogee Prakasham,
Vergé Daniel,
Hanoun Naïma,
Brisorgueil MarieJeanne,
Hen René,
Lesch KlausPeter,
Hamon Michel,
Miquel MarieChristine
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2004.03194.x
Subject(s) - serotonergic , serotonin , serotonin transporter , 5 ht receptor , raphe , biology , serotonin plasma membrane transport proteins , endocrinology , raphe nuclei , dorsal raphe nucleus , neuroscience , medicine , neurite , receptor , biochemistry , in vitro
Serotonin 5‐HT 1A and 5‐HT 1B 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‐HT 1A R−/− and 5‐HT 1B R−/− 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‐HT 1A R−/− 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‐HT 1A autoreceptors. Together, these data suggest that serotonin autoreceptors, mainly 5‐HT 1A but also 5‐HT 1B , 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.