Enhancement of the FGFR1 signaling in the FGFR1-5-HT1A heteroreceptor complex in midbrain raphe 5-HT neuron systems. Relevance for neuroplasticity and depression

• Published in: Biochemical and biophysical research communications 2015-07, Vol.463 (3), p.180-186
• Main Authors: Borroto-Escuela, Dasiel O., Pérez-Alea, Mileidys, Narvaez, Manuel, Tarakanov, Alexander O., Mudó, Giuseppa, Jiménez-Beristain, Antonio, Agnati, Luigi F., Ciruela, Francisco, Belluardo, Natale, Fuxe, Kjell
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - administration & dosage; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Animals; Cell Line; Depression; Dimerization; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblast Growth Factor 2 - administration & dosage; Fibroblast Growth Factor 2 - pharmacology; Fibroblast growth factor receptor; Heteroreceptor complex; Medicin och hälsovetenskap; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - physiology; Neuronal plasticity; Neuronal Plasticity - drug effects; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Phosphorylation - drug effects; Protein Interaction Maps; Rats; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Receptor, Serotonin, 5-HT1A - metabolism; Serotonin - metabolism; Serotonin 5-HT1 Receptor Agonists - administration & dosage; Serotonin 5-HT1 Receptor Agonists - pharmacology; Serotonin 5-HT1A receptor
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2015.04.133

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. •Synergistic FGFR1-5HT1A interactions exist in FGFR1 signalling of the RN33B cells.•Synergistic FGFR1-5HT1A interactions exist in ERK1/2 signalling of the RN33B cells.•Synergistic FGFR1-5HT1A interactions exist in structure plasticity of the RN33B cells.•Synergistic FGFR1-5HT1A interactions exist in FGFR1 signalling in the raphe midbrain.•Synergistic FGFR1-5HT1A interactions exist in ERK1/2 signalling in the raphe midbrain.