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Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the dentate gyrus are related with antidepressant-like effects

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Abstract

Galanin (GAL) and the NPYY1 agonist play a role in mood regulation and both neuropeptides interact in several central functions. The present study examined the interaction between Galanin receptor 2 (GALR2) and Neuropeptide Y Y1 receptor (NPYY1R) in the dentate gyrus (DG) of the Hippocampus in relation to depression-like behavior. Using receptor autoradiography, in situ hybridization and in situ proximity ligation assay an interaction between GALR and NPYY1R was demonstrated in the DG probably involving the formation of GALR2-NPYY1R heteroreceptor complexes. These complexes were specifically observed in the polymorphic and subgranular subregions of the DG, where both receptors were found to colocalize. Moreover, this GALR2/NPYY1R interaction was linked to an enhancement of the antidepressive-like behavior mediated by NPYY1R in the forced swimming test. Specific cells populations within DG subregions may be involved in this behavioral effect since the coactivation of GALR2 and NPYY1R enhances the NPYY1R-mediated reduction in the number of c-Fos immunoreactive nuclei in the polymorphic region. These results indicate that GALR2/NPYY1R interactions can provide a novel integrative mechanism in DG in depression-related behavior and may give the basis for the development of drugs targeting GALR2/NPYY1R heteroreceptor complexes in the DG of the hippocampus for the treatment of depression.

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Acknowledgments

This work has been supported by Junta de Andalucia CVI-6476, the Karolinska Institutets Forskningsstiftelser 2014/2015 to D.O.B-E, by the Swedish Medical Research Council (62X-00715-50-3) and AFA Försäkring (130328) to KF and D.O.B-E. All authors contributed to and have approved the final manuscript.

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  1. Departamento de Fisiología Humana, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Campus de Teatinos s/n., 29071, Málaga, Spain

    Manuel Narváez, Carmelo Millón, Belén Gago, Antonio Flores-Burgess, José Angel Narváez & Zaida Díaz-Cabiale

  2. Department of Neuroscience, Karolinska Institute, Stockholm, Sweden

    Dasiel O. Borroto-Escuela & Kjell Fuxe

  3. Universidad de Málaga, Instituto de Investigación Biomédica de Málaga, Facultad de Psicología, Campus de Teatinos S/n, 29071, Málaga, Spain

    Luis Santín

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  1. Manuel Narváez
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  2. Dasiel O. Borroto-Escuela
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  3. Carmelo Millón
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Correspondence to Manuel Narváez.

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Narváez, M., Borroto-Escuela, D.O., Millón, C. et al. Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the dentate gyrus are related with antidepressant-like effects. Brain Struct Funct 221, 4129–4139 (2016). https://doi.org/10.1007/s00429-015-1153-1

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