2026-05-28T22:56:18Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/414192026-02-03T10:50:36Zcom_10630_2254col_10630_37953

Intracerebroventricular knockdown of NPY1R disrupts NPY1R-GALR2/TrkB heteroreceptor complexes without affecting neuroplasticity or depressive-like behaviour Moreno-Madrid, Isabel Arrabal-Gómez, Carlos Romero-Imbroda, Jesús Díaz-Casares, Amelia Fuxe, Kjell Borroto Escuela, Dasiel Óscar Serrano-Castro, Pedro Jesús Narváez-Peláez, Manuel Neurorreceptores Receptores celulares Neuroplasticidad Hipocampo (Cerebro) Depresión mental Background:Neuropeptide Y1 receptor (NPY1R) heteroreceptor complexes with galanin receptor 2 (GALR2) and Tropomyosin receptor kinase B (TrkB) contribute to neuroplasticity and mood regulation. Aims:To determine whether transient intracerebroventricular (ICV) knockdown of NPY1R is sufficient to alter hippocampal neurogenesis and depressive-like behaviour. Methods:Adult Sprague-Dawley rats received a single ICV injection of Accell Smart-Pool small interfering RNA (siRNA) targeting NPY1R or a scrambled control. NPY1R protein levels, NPY1R-GALR2 and NPY1R-TrkB complexes (in situ proximity ligation), proliferating cell nuclear antigen (PCNA) counts, brain-derived neurotrophic factor (BDNF) expression and forced-swim behaviour were assessed 6, 8 and 10 days post-injection in the ventral hippocampus. Results:ICV siRNA significantly reduced NPY1R immunoreactivity (peak at day 8; p<0.05) and lowered NPY1R-GALR2 and NPY1R-TrkB heteroreceptor complexes (p<0.01 and p<0.001, respectively). PCNA-positive cell numbers and BDNF optical density were unchanged at all time points. Forced-swim immobility, climbing and swimming times likewise remained unaltered. Conclusions:Transient ICV knockdown effectively disrupts NPY1R heteroreceptor complexes but fails to impact neurogenesis or depressive-like behaviour, indicating compensatory mechanisms that preserve hippocampal plasticity. Within the time window and conditions tested, transient NPY1R knockdown disrupted GALR2/TrkB heteroreceptor complexes without altering neurogenesis or depressive-like behaviour, delineating receptor-complex-level target engagement and motivating studies using sustained and circuit-specific manipulations to assess therapeutic potential. 2026-01-12T09:52:36Z 2026-01-12T09:52:36Z 2026-01-12T09:52:36Z 2025-11-27 journal article Moreno-Madrid, I., Arrabal-Gómez, C., Romero-Imbroda, J., Díaz-Casares, A., Fuxe, K., Borroto-Escuela, D., ... & Narváez, M. (2025). Intracerebroventricular knockdown of NPY1R disrupts NPY1R-GALR2/TrkB heteroreceptor complexes without affecting neuroplasticity or depressive-like behaviour. Journal of Psychopharmacology, 02698811251389528. https://hdl.handle.net/10630/41419 10.1177/02698811251389528 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Sage