Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression
The FGFR1-5-HT1A heteroreceptor complexes are involved in neuroplasticity in the rat hippocampus and in the mesencephalic raphe 5-HT nerve cells. There exists a 5-HT1A protomer enhancement of FGFR1 protomer signaling. Acute and 10 day treatment with intracerebroventricular (i.c.v.) FGF-2 and the 5-H...
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Frontiers Media S.A.
2017-10-01
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Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00309/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dasiel O. Borroto-Escuela Dasiel O. Borroto-Escuela Dasiel O. Borroto-Escuela Caitlin M. DuPont Xiang Li David Savelli David Savelli Davide Lattanzi Ipsit Srivastava Manuel Narváez Michael Di Palma Elisa Barbieri Yuniesky Andrade-Talavera Riccardo Cuppini Yuji Odagaki Miklos Palkovits Patrizia Ambrogini Maria Lindskog Kjell Fuxe |
spellingShingle |
Dasiel O. Borroto-Escuela Dasiel O. Borroto-Escuela Dasiel O. Borroto-Escuela Caitlin M. DuPont Xiang Li David Savelli David Savelli Davide Lattanzi Ipsit Srivastava Manuel Narváez Michael Di Palma Elisa Barbieri Yuniesky Andrade-Talavera Riccardo Cuppini Yuji Odagaki Miklos Palkovits Patrizia Ambrogini Maria Lindskog Kjell Fuxe Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression Frontiers in Cellular Neuroscience fibroblast growth factor receptor 1 5-HT1A receptor heteroreceptor complexes depression hippocampus raphe |
author_facet |
Dasiel O. Borroto-Escuela Dasiel O. Borroto-Escuela Dasiel O. Borroto-Escuela Caitlin M. DuPont Xiang Li David Savelli David Savelli Davide Lattanzi Ipsit Srivastava Manuel Narváez Michael Di Palma Elisa Barbieri Yuniesky Andrade-Talavera Riccardo Cuppini Yuji Odagaki Miklos Palkovits Patrizia Ambrogini Maria Lindskog Kjell Fuxe |
author_sort |
Dasiel O. Borroto-Escuela |
title |
Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression |
title_short |
Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression |
title_full |
Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression |
title_fullStr |
Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression |
title_full_unstemmed |
Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression |
title_sort |
disturbances in the fgfr1-5-ht1a heteroreceptor complexes in the raphe-hippocampal 5-ht system develop in a genetic rat model of depression |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular Neuroscience |
issn |
1662-5102 |
publishDate |
2017-10-01 |
description |
The FGFR1-5-HT1A heteroreceptor complexes are involved in neuroplasticity in the rat hippocampus and in the mesencephalic raphe 5-HT nerve cells. There exists a 5-HT1A protomer enhancement of FGFR1 protomer signaling. Acute and 10 day treatment with intracerebroventricular (i.c.v.) FGF-2 and the 5-HT1A agonist 8-OH-DPAT produced enhanced antidepressant effects in the forced swim test (FST). We studied in the current work the disturbances in the FGFR1-5-HT1A heterocomplexes in a genetic rat model of depression, the Flinders sensitive line (FSL) rats of Sprague-Dawley (SD) origin, by means of neurochemical, neurophysiological and behavioral techniques. In control SD rats, the FGFR1 agonist SUN11602 and FGF2 produced a significant reduction of G protein-coupled inwardly rectifying K+ channel (GIRK) currents induced by 8-OH-DPAT in the CA1 area of the hippocampus. In FSL rats, only i.c.v. 8-OH-DPAT alone treatment produced a significant reduction in the immobility time. The combined i.c.v. treatment (FGF2 + 8-OH-DPAT) in FSL rats did not cause a significant decrease in immobility time in the FST. However, in the SD rats this combined treatment produced a significant reduction. Furthermore, in the FSL rat a significant increase in the density of FGFR1-5-HT1A proximity ligation assay (PLA) positive clusters was only found after i.c.v. 8-OH-DPAT treatment alone in the CA2 and CA3 areas. In the SD rat a significant increase in the density of specific PLA clusters was only observed in the CA2 area of the i.c.v. combined treatment (FGF2 + 8-OH-DPAT) group. No treatment led to significant changes in the PLA clusters of the dorsal raphe in the FSL rat. However, significant changes in the density of specific PLA clusters were only found in the dorsal raphe of SD rats after combined treatment and treatment with 8-OH-DPAT alone. The results indicate that in FSL rats compared with SD rats alterations may develop in the ability of 8-OH-DPAT and combined FGFR1 and 5-HT1A agonist treatment to increase the density of FGFR1-5-HT1A heteroreceptor complexes of the dorsal raphe. It is proposed that such deficits in FSL rats may possibly reflect a failure of the combined agonist treatment to uncouple the 5-HT1A autoreceptors from the GIRK channels. This may contribute to the failure of producing antidepressant-like effects in the FSL rat by combined agonist treatment as seen in the SD rat. The antidepressant-like effects seen with the 5-HT1A agonist alone treatment in FSL but not in SD rats may instead involve significant increases in the FGFR1-5-HT1A complexes of the CA2 and CA3 areas of the hippocampus. |
topic |
fibroblast growth factor receptor 1 5-HT1A receptor heteroreceptor complexes depression hippocampus raphe |
url |
http://journal.frontiersin.org/article/10.3389/fncel.2017.00309/full |
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doaj-6c7d2dceab9b42ec8eef5631d9ea14fc2020-11-24T20:45:57ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-10-011110.3389/fncel.2017.00309289847Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe-Hippocampal 5-HT System Develop in a Genetic Rat Model of DepressionDasiel O. Borroto-Escuela0Dasiel O. Borroto-Escuela1Dasiel O. Borroto-Escuela2Caitlin M. DuPont3Xiang Li4David Savelli5David Savelli6Davide Lattanzi7Ipsit Srivastava8Manuel Narváez9Michael Di Palma10Elisa Barbieri11Yuniesky Andrade-Talavera12Riccardo Cuppini13Yuji Odagaki14Miklos Palkovits15Patrizia Ambrogini16Maria Lindskog17Kjell Fuxe18Division of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, ItalyGrupo Bohío-Estudio, Observatorio Cubano de Neurociencias, Yaguajay, CubaDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, ItalyDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenInstituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Málaga, SpainDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, ItalyDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenNeuronal Oscillations Laboratory, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Stockholm, SwedenDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, ItalyDepartment of Psychiatry, Faculty of Medicine, Saitama Medical University, Saitama, JapanDepartment of Anatomy, Histology and Embryology, Semmelweis University, Budapest, HungaryDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, ItalyDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenDivision of Cellular and Molecular Neurochemistry, Department of Neuroscience, Karolinska Institutet, Stockholm, SwedenThe FGFR1-5-HT1A heteroreceptor complexes are involved in neuroplasticity in the rat hippocampus and in the mesencephalic raphe 5-HT nerve cells. There exists a 5-HT1A protomer enhancement of FGFR1 protomer signaling. Acute and 10 day treatment with intracerebroventricular (i.c.v.) FGF-2 and the 5-HT1A agonist 8-OH-DPAT produced enhanced antidepressant effects in the forced swim test (FST). We studied in the current work the disturbances in the FGFR1-5-HT1A heterocomplexes in a genetic rat model of depression, the Flinders sensitive line (FSL) rats of Sprague-Dawley (SD) origin, by means of neurochemical, neurophysiological and behavioral techniques. In control SD rats, the FGFR1 agonist SUN11602 and FGF2 produced a significant reduction of G protein-coupled inwardly rectifying K+ channel (GIRK) currents induced by 8-OH-DPAT in the CA1 area of the hippocampus. In FSL rats, only i.c.v. 8-OH-DPAT alone treatment produced a significant reduction in the immobility time. The combined i.c.v. treatment (FGF2 + 8-OH-DPAT) in FSL rats did not cause a significant decrease in immobility time in the FST. However, in the SD rats this combined treatment produced a significant reduction. Furthermore, in the FSL rat a significant increase in the density of FGFR1-5-HT1A proximity ligation assay (PLA) positive clusters was only found after i.c.v. 8-OH-DPAT treatment alone in the CA2 and CA3 areas. In the SD rat a significant increase in the density of specific PLA clusters was only observed in the CA2 area of the i.c.v. combined treatment (FGF2 + 8-OH-DPAT) group. No treatment led to significant changes in the PLA clusters of the dorsal raphe in the FSL rat. However, significant changes in the density of specific PLA clusters were only found in the dorsal raphe of SD rats after combined treatment and treatment with 8-OH-DPAT alone. The results indicate that in FSL rats compared with SD rats alterations may develop in the ability of 8-OH-DPAT and combined FGFR1 and 5-HT1A agonist treatment to increase the density of FGFR1-5-HT1A heteroreceptor complexes of the dorsal raphe. It is proposed that such deficits in FSL rats may possibly reflect a failure of the combined agonist treatment to uncouple the 5-HT1A autoreceptors from the GIRK channels. This may contribute to the failure of producing antidepressant-like effects in the FSL rat by combined agonist treatment as seen in the SD rat. The antidepressant-like effects seen with the 5-HT1A agonist alone treatment in FSL but not in SD rats may instead involve significant increases in the FGFR1-5-HT1A complexes of the CA2 and CA3 areas of the hippocampus.http://journal.frontiersin.org/article/10.3389/fncel.2017.00309/fullfibroblast growth factor receptor 15-HT1A receptorheteroreceptor complexesdepressionhippocampusraphe |