RT Journal Article
T1 Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus
A1 Borroto Escuela, Dasiel Óscar
A1 Pita-Rodríguez, Mariana
A1 Fores-Pons, Ramón
A1 Barbancho-Fernández, Miguel Ángel
A1 Fuxe, Kjell
A1 Narváez-Peláez, Manuel
K1 Neuropéptidos
K1 Receptores de neurotransmisores
K1 Depresión mental
AB A need for new antidepressants is necessary since traditional antidepressants have several flaws. Neuropeptide Y(NPY) Y1 receptor (NPYY1R) and galanin (GAL) receptor 2 (GALR2) interact in several regions of the limbic system, including the hippocampus. The current study assesses the antidepressant effects induced by GALR2 and NPYY1R coactivation, together with the evaluation of cell proliferation through 5-Bromo-2'-deoxyuridine expression within the dentate gyrus of the ventral hippocampus (vDG). We employed in situ proximity ligation assay to manifest GALR2/NPYY1R heteroreceptor complexes. Additionally, the expression pattern of GALR2 and the activation of the extracellular-regulated kinases (ERK) pathway after GALR2 and NPYY1R costimulation in cell cultures were examined. GALR2 and NPYY1R coactivation resulted in sustained antidepressant behaviors in the FST after 24 h, linked to increased cell proliferation in the vDG. Moreover, an increased density of GALR2/NPYY1R heteroreceptor complexes was observed in vDG, on doublecortin-expressing neuroblasts. Recruitment of the GALR2 expression to the plasma membrane was observed upon the coactivation of GALR2 and NPYY1R in cell cultures, presumably associated to the enhanced effects on the activation of ERK pathway. GALR2 may promote the GALR2/NPYY1R heteroreceptor complexes formation in the ventral hippocampus. It may induce a transformation of cell proliferation toward a neuronal lineage by enhancement of ERK pathway. Thus, it may give the mechanism for the antidepressant behavior observed. These results may provide the basis for the development of heterobivalent agonist pharmacophores, targeting GALR2/NPYY1R heteromers, especially in the neuronal precursor cells of the dentate gyrus in the ventral hippocampus for the novel treatment of depression.
PB Wiley
YR 2021
FD 2021-02-21
LK https://hdl.handle.net/10630/36932
UL https://hdl.handle.net/10630/36932
LA eng
NO Borroto-Escuela DO, Pita-Rodriguez M, Fores-Pons R, Barbancho MA, Fuxe K, Narváez M. Galanin and Neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus. J Cell Physiol. 2021; 236: 3565–3578. https://doi.org/10.1002/jcp.30092
NO https://openpolicyfinder.jisc.ac.uk/id/publication/13864
NO The study was supported by the UMA18‐FEDERJA‐100 and Proyecto Puente UMA, Spain to Manuel Narváez, by the Swedish Medical Research Council, Sweden (62X‐00715‐50‐3) and Parkinson Fonden, Sweden to Kjell Fuxe, and by Hjärnfonden, Sweden (F02018‐0286), Hjärnfonden, Sweden (F02019‐0296), and Karolinska Institutet Forskningsstiftelser, Sweden, to Dasiel O. Borroto‐Escuela.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026