title: Enhancement of the FGFR1 signaling in the FGFR1-5-HT1A heteroreceptor complex in midbrain raphe 5-HT neuron systems. Relevance for neuroplasticity and depression.
abstract: New findings show existence of FGFR1-5-HT1A heteroreceptor complexes in 5-HT nerve cells of the dorsal and median raphe nuclei of the rat midbrain and hippocampus. Synergistic receptor-receptor interactions in these receptor complexes indicated their enhancing role in hippocampal plasticity. The existence of FGFR1-5-HT1A heteroreceptor complexes also in midbrain raphe 5-HT nerve cells open up the possibility that antidepressant drugs by increasing extracellular 5-HT levels can cause an activation of the FGF-2/FGFR1 mechanism in these nerve cells as well. Therefore, the agonist modulation of the FGFR1-5-HT1A heteroreceptor complexes and their specific role is now determined in rat medullary raphe RN33B cells and in the caudal midline raphe area of the midbrain rich in 5-HT nerve cells. The combined i.c.v. treatment with FGF-2 and the 5-HT1A agonist 8-OHDPAT synergistically increased FGFR1 and ERK1/2 phosphorylation in the raphe midline area of the midbrain and in the RN33B cells. Cotreatment with FGF2 and the 5-HT1A agonist induced RN33B cell differentiation as seen from development of an increased number and length of extensions per cell and their increased 5-HT immunoreactivity. These signaling and differentiation events were dependent on the receptor interface since they were blocked by incubation with TMV but not by TMII of the 5-HT1A receptor. Taken together, the 5-HT1A autoreceptors by being part of a FGFR1-5-HT1A heteroreceptor complex in the midbrain raphe 5-HT nerve cells appears to have also a trophic role in the central 5-HT neuron systems besides playing a key role in reducing the firing of these neurons.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Dasiel.Borroto-Escuela@ki.se.
authors.forename: Dasiel O
authors.initials: DO
authors.lastname: Borroto-Escuela
authors.affiliation: Lab Animal Models and Cancer Laboratory Anatomy Pathology Program, Institut de Recerca Vall d'Hebron, 08035 Barcelona, Spain. Electronic address: mileidys.perez@vhir.org.
authors.forename: Mileidys
authors.initials: M
authors.lastname: Pérez-Alea
authors.affiliation: Department of Physiology, School of Medicine, University of Málaga, Spain. Electronic address: mnarvaez@uma.es.
authors.forename: Manuel
authors.initials: M
authors.lastname: Narvaez
authors.affiliation: Russian Academy of Sciences, St. Petersburg Institute for Informatics and Automation, Saint Petersburg, Russia. Electronic address: tar@iias.spb.su.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Tarakanov
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Molecular Neurobiology, University of Palermo, Palermo, Italy. Electronic address: g.mudo@unipa.it.
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Mudó
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Tony.jimenez-beristain@ki.se.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jiménez-Beristain
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: luigiagnati@tin.it.
authors.forename: Luigi F
authors.initials: LF
authors.lastname: Agnati
authors.affiliation: Unitat de Farmacologia, Departament Patologia i Terapèutica Experimental, Universitat de Barcelona, Spain. Electronic address: fciruela@ub.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Ciruela
authors.affiliation: Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Molecular Neurobiology, University of Palermo, Palermo, Italy. Electronic address: n.belluardo@unipa.it.
authors.forename: Natale
authors.initials: N
authors.lastname: Belluardo
authors.affiliation: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Electronic address: Kjell.Fuxe@ki.se.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D060066:Protein Interaction Maps; D051381:Rats; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D058825:Serotonin 5-HT1 Receptor Agonists; D016222:Fibroblast Growth Factor 2; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D051496:Receptor, Fibroblast Growth Factor, Type 1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Depression; Dimerization; Fibroblast growth factor receptor; Heteroreceptor complex; Neuronal plasticity; Serotonin 5-HT1A receptor