RT Journal Article
T1 Intranasal Delivery of Galanin 2 and Neuropeptide Y1 Agonists Enhanced Spatial Memory Performance and Neuronal Precursor Cells Proliferation in the Dorsal Hippocampus in Rats.
A1 Borroto Escuela, Dasiel Óscar
A1 Fores, Ramón
A1 Pita-Rodríguez, Mariana
A1 Barbancho-Fernández, Miguel Ángel
A1 Zamorano-González, Pablo
A1 García-Casares, Natalia
A1 Fuxe, Kjell
A1 Narváez-Peláez, Manuel
K1 Alzheimer, Enfermedad de - Modelos animales
K1 Demencia
AB A need for new therapeutic approaches are necessary for dementia conditions and memory deficits of different origins, such as Alzheimer’s disease. There is complex pathophysiological mechanisms involved, affecting adult hippocampal neurogenesis, in which neuropeptides and its neurogenesis regulation seem to participate. Neuropeptide Y(NPY) Y1 receptor (Y1R) and galanin (GAL) receptor 2 (GALR2) interact in brain regions responsible for learning and memory processes, emphasizing the hippocampus. Moreover, a significant challenge for treatments involving peptide drugs is bypassing the blood-brain barrier. The current study assesses the sustained memory performance induced by GALR2 and NPYY1R agonists intranasal coadministration and their neurochemical hippocampal correlates. Memory retrieval was conducted in the object-in-place task together with in situ proximity ligation assay (PLA) to manifest the formation of GALR2/Y1R heteroreceptor complexes and their dynamics under the different treatments. We evaluated cell proliferation through a 5-Bromo-2’-deoxyuridine (BrdU) expression study within the dentate gyrus of the dorsal hippocampus. The GalR2 agonist M1145 was demonstrated to act with the Y1R agonist to improve memory retrieval at 24 hours in the object-in-place task. Our data show that the intranasal administration is a feasible technique for directly delivering Galanin or Neuropeptide Y compounds into CNS. Moreover, we observed the ability of the co-agonist treatment to enhance the cell proliferation in the DG of the dorsal hippocampus through 5- Bromo-2’-deoxyuridine (BrdU) expression analysis at 24 hours. The understanding of the cellular mechanisms was achieved by analyzing the GALR2/Y1R heteroreceptor complexes upon agonist coactivation of their two types of receptor protomers in Doublecortin-expressing neuroblasts. Our results may provide the basis for developing heterobivalent agonist pharmacophores, targeting GALR2-Y1R heterocomplexes.
PB Frontiers
YR 2022
FD 2022
LK https://hdl.handle.net/10630/36711
UL https://hdl.handle.net/10630/36711
LA eng
NO Borroto-Escuela DO, Fores R, Pita M, Barbancho MA, Zamorano-Gonzalez P, Casares NG, Fuxe K and Narváez M (2022) Intranasal Delivery of Galanin 2 and Neuropeptide Y1 Agonists Enhanced Spatial Memory Performance and Neuronal Precursor Cells Proliferation in the Dorsal Hippocampus in Rats. Front. Pharmacol. 13:820210. doi: 10.3389/fphar.2022.820210
NO The work was supported by the UMA18-FEDERJA-100 and Proyecto Jovenes Investigadores (B1-2019_04) and Proyecto Puente (B4-2021) UMA , Spain to MN. This work was also supported by the Swedish Medical Research Council, Sweden (No. 62X-00715-50-3) to KF, by Stiftelsen Olle Engkvist Byggmästare to KF and by Hjärnfonden, Sweden (No. F02018-0286), Hjärnfonden, Sweden (No. F02019-0296) and Karolinska Institutet Forskningsstiftelser, Sweden to DB-E. DB-E belongs to the “Academia de Biólogos Cubanos” group, Cuba. Special mention to Grupo Vithas.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026