Up-regulation of the neuronal serotoninergic phenotype in vitro: BDNF and cAMP share Trk B-dependent mechanisms.
The effects of brain-derived neurotrophic factor (BDNF) and cAMP on the neuronal serotoninergic phenotype were studied in primary cultures of E14 rat embryonic rostral raphe. Short treatments (for 18 h) with BDNF or dibutyryl-cAMP induced an almost two-fold increase in the number of serotoninergic neurones and a dramatic extension and ramification of their neurites. These changes were associated with marked increases in the levels of mRNAs encoding the serotonin transporter, the 5-HT1A and 5-HT1B receptors and the BDNF receptor tyrosine kinase B (TrkB). Concomitant blockade of tyrosine kinases by genistein suppressed all the up-regulating effects of BDNF and cAMP on 5-hydroxytryptamine (5-HT) neurones. These findings suggest that an auto-amplifying mechanism underlies the promoting effect of BDNF on the differentiation of serotoninergic neurones through TrkB activation, which is also triggered by cAMP.
Rumajogee
Prakasham
P
Laboratoire de Neurobiologie des Signaux Intercellulaires, CNRS UMR 7101, Université Pierre et Marie Curie, Paris, France.
Madeira
Alexandra
A
Vergé
Daniel
D
Hamon
Michel
M
Miquel
Marie-Christine
MC
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D003994:Bucladesine; D019833:Genistein; D000242:Cyclic AMP; D020813:Receptor, trkB