RT Journal Article
T1 Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus
A1 Arrabal-Gómez, Carlos
A1 Serrano-Castro, Pedro
A1 Sánchez-Pérez, José Andrés
A1 Garcia-Casares, Natalia
A1 Fuxe, Kjell
A1 Borroto Escuela, Dasiel Óscar
A1 Narváez, Manuel
K1 Depresión - Tratamiento
AB Background: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. Research Design and Methods: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i.n.) routes. The Forced Swimming Test (FST) was employed to assess antidepressant-like activity, while in situ Proximity Ligation Assay and immunohistochemistry were used to examine NPY1R/TrkB heteroreceptor complexes and BDNF expression in the ventral dentate gyrus (DG), along with neurogenesis markers.Results: The combined treatment significantly reduced immobility in the FST, indicative of enhanced antidepressant-like effects, correlated with increased formation of NPY1R/TrkB complex and brainderivedneurotrophic factor (BDNF) expression in the ventral DG. These molecular alterations were associated with increased neurogenesis.Conclusions: The coadministration of an NPY1R agonist and Ketamine in a rodent model demonstratedpotentiated antidepressant responses through synergistic neurobiological pathways, including TrkB signaling and hippocampal neurogenesis. This indicates a novel therapeutic strategy for MDD, warranting further clinical investigation to fully understand its implications.
PB Taylor & Francis
YR 2024
FD 2024-04-18
LK https://hdl.handle.net/10630/33389
UL https://hdl.handle.net/10630/33389
LA eng
NO Carlos Arrabal-Gómez, Pedro Serrano-Castro, Jose Andrés Sánchez- Pérez, Natalia Garcia-Casares, Kjell Fuxe, Dasiel Borroto-Escuela & Manuel Narváez (2024) Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus, Expert Opinion on Therapeutic Targets, 28:4, 309-322, DOI: 10.1080/14728222.2024.2342524
NO This manuscript was funded by the UMA18-FEDERJA-100 and ProyExcel_00613, Junta de Andalucía, Spain, to MN. Funding for open access charge: Universidad de Málaga/CBUA. Additional funding supportcame from Cátedra Imbrain: Neurociencia Integrada y Bionestar to MN.This work also received support from Stiftelsen Olle Engkvist Byggmästare in 2018 and 2021, as well as from the Swedish Medical Research Council (Grant No. 62X-00715-50-3) awarded to KF and DB-E. Additionally, funding was provided by Hjärnfonden (Grants F02018-0286 and F02019-0296), Karolinska Institutet Forskningsstiftelser 2022, EMERGIA 2020-39318 (Plan Andaluz de Investigación, Desarrollo e Innovación 2020), an  CONSOLIDACION INVESTIGADORA (CNS2022-136008, Programa Estatal para Desarrollar, Atraer y Retener Talento, del Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023) awarded to DB-E. DB-E is affiliated with the Academia de Biólogos Cubanos and the Observatorio Cubano de Neurociencias (Yaguajay, Cuba).
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026