PMID- 10833301 OWN - NLM STAT- MEDLINE DCOM- 20000727 LR - 20151119 IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 15 IP - 5 DP - 2000 May TI - Sequential activation of the 5-HT1(A) serotonin receptor and TrkB induces the serotonergic neuronal phenotype. PG - 446-55 AB - Serotonin (5-HT) is an important factor controlling survival, differentiation, and plasticity of neurons in serotonergic target regions of the brain and has been implicated in major psychiatric and autonomic disorders. Relatively little is known, however, of factors controlling differentiation and plasticity of developing and adult 5-HT neurons. We show now that 5-HT, the 5-HT1(A) receptor, brain-derived neurotrophic factor (BDNF), and its receptor, trkB, form an auto/paracrine loop for the regulation of the serotonergic phenotype. Serotonin applied to cultures from E14 rat raphe increased numbers of neurons expressing serotonergic markers in a dose-dependent manner. Agonists of the 5-HT1(A) receptor, BP-554 and 8-OH-DPAT, but not agonists of the 5-HT1(B) and 5-HT1(D) receptors, mimicked this effect, while the specific 5-HT1(A) antagonist, WAY-100635, inhibited it. Serotonin also increased BDNF mRNA and protein in embryonic raphe cultures. Induction of serotonergic markers by serotonin was suppressed by a trkB-IgG fusion protein but not by trkC-IgG. Taken together, our data indicate that serotonin acts on 5-HT1(A) autoreceptors, causing up-regulation of BDNF, which activates trkB to promote serotonergic phenotype-specific markers. CI - Copyright 2000 Academic Press. FAU - Galter, D AU - Galter D AD - Department of Neuroanatomy, University of Heidelberg, Germany. FAU - Unsicker, K AU - Unsicker K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Biomarkers) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Enzyme Inhibitors) RN - 0 (Indole Alkaloids) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Serotonin) RN - 0 (Receptors, Serotonin, 5-HT1) RN - 0 (Serotonin Receptor Agonists) RN - 333DO1RDJY (Serotonin) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.- (Phosphotransferases) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) SB - IM MH - Animals MH - Biomarkers MH - Brain-Derived Neurotrophic Factor/genetics MH - Carbazoles/pharmacology MH - Cells, Cultured MH - Enzyme Inhibitors/pharmacology MH - Indole Alkaloids MH - Neurons/*physiology MH - Phenotype MH - Phosphotransferases/antagonists & inhibitors MH - RNA, Messenger/metabolism MH - Raphe Nuclei/cytology/drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, trkB/*physiology MH - Receptor, trkC/physiology MH - Receptors, Serotonin/*physiology MH - Receptors, Serotonin, 5-HT1 MH - Serotonin/pharmacology/*physiology MH - Serotonin Receptor Agonists/pharmacology EDAT- 2000/06/02 00:00 MHDA- 2000/06/02 00:01 CRDT- 2000/06/02 00:00 PHST- 2000/06/02 00:00 [pubmed] PHST- 2000/06/02 00:01 [medline] PHST- 2000/06/02 00:00 [entrez] AID - S1044-7431(00)90841-8 [pii] AID - 10.1006/mcne.2000.0841 [doi] PST - ppublish SO - Mol Cell Neurosci. 2000 May;15(5):446-55. doi: 10.1006/mcne.2000.0841.