Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition

Rasiel Beltran-Casanueva; Aracelis Hernández-García; Paula de Amo García; Encarnación Blanco-Reina; Pedro Serrano-Castro; Natalia García-Casares; Kjell Fuxe; Dasiel O Borroto-Escuela; Manuel Narváez

doi:10.3389/fncel.2024.1323986

Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition

Front Cell Neurosci. 2024 Feb 14:18:1323986. doi: 10.3389/fncel.2024.1323986. eCollection 2024.

Authors

Rasiel Beltran-Casanueva^{1

2}, Aracelis Hernández-García^{1

2

3}, Paula de Amo García⁴, Encarnación Blanco-Reina⁴, Pedro Serrano-Castro^{4

5

6}, Natalia García-Casares⁴, Kjell Fuxe^#¹, Dasiel O Borroto-Escuela^#^{1

2}, Manuel Narváez^#^{4

5}

Affiliations

¹ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
² Receptomics and Brain Disorders Lab, Facultad de Medicina, Edificio Lopez-Peñalver, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Spain.
³ Departamento de Docencia e Investigación, Universidad de Ciencias Médicas de Holguín, Hospital Pedíatrico Universitario Octavio de la Concepción de la Pedraja, Holguín, Cuba.
⁴ Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain.
⁵ Grupo Hospitalario Vithas, Vithas Málaga, Málaga, Spain.
⁶ Unit of Neurology, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario de Málaga, Málaga, Spain.

^# Contributed equally.

Abstract

Introduction: This study may unveil novel insights into the interactions between neuropeptide Y receptor 1 (NPY1R) and galanin receptor 2 (GALR2), in the dentate gyrus of the dorsal hippocampus, shedding light on their role in neurogenesis and cognitive functions. Existing literature highlights the potential of these interactions in enhancing learning and memory, yet detailed mechanisms remain underexplored.

Methods: Utilizing intracerebroventricular injections of GALR2 and NPY1R agonists in Sprague-Dawley male rats, we examined neurogenesis via markers PCNA and DCX, and memory consolidation through the object-in-place task over a three-week period.

Results: Significant increases in NPY1R-GALR2 co-localization and neuroblast proliferation were observed, alongside enhanced memory consolidation. These findings suggest a synergistic effect of NPY1R and GALR2 activation on cognitive functions.

Discussion: Our findings may foster the development of novel heterobivalent or multitargeting drugs, affecting NPY1R-GALR2 interaction, and suggest a future pharmacogical strategy for improving learning and memory found in many brain diseases. Further research is encouraged to explore these mechanisms in pathological models.

Keywords: GALR2 agonist; NPY1R agonist; cognitive enhancement; neurogenic enhancement; neuronal proliferation; spatial memory performance.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the UMA18-FEDERJA-100 and ProyExcel_00613, Junta de Andalucía, Spain, to MN. Beca de Iniciación a la investigación de la Universidad de Málaga to PA. Funding for open access charge: Universidad de Málaga/CBUA. Additional funding support came 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), and 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).