Enhancing Cognitive Functions and Neuronal Growth through NPY1R Agonist and Ketamine Co-Administration: Evidence for NPY1R-TrkB Heteroreceptor Complexes in Rats.
Carlos Arrabal-Gómez, Rasiel Beltran-Casanueva, Aracelis Hernández-García, Juan Vicente Bayolo-Guanche, Miguel Angel Barbancho-Fernández, Pedro Jesús Serrano-Castro, Manuel Narváez
Cells April 12, 2024 DOI: 10.3390/cells13080669 via PubMed
Summary
AI-generated from the abstractA single dose combining a neuropeptide Y Y1 receptor agonist with ketamine enhanced memory consolidation and increased production of new neurons (neuroblasts) in the dorsal hippocampus of male rats, without affecting quiescent neural progenitors or astrocytes. The effects were linked to brain-derived neurotrophic factor and suggested the formation of NPY1R-TrkB heteroreceptor complexes, though this interaction requires further confirmation. The findings point to a potential therapeutic approach for neurodegenerative diseases.
Study at a glance
| Characteristics | Controlled laboratory experiment Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | [Leu31-Pro34]NPY Ketamine |
| Dose | 132 µg of [Leu31-Pro34]NPY and 10 mg/kg of Ketamine |
| Duration | Single-dose administration, assessed 24 h after treatment |
| Topics | Ketamine |
| Keywords | Npy1r agonist Npy1r-trkb heteroreceptor complex Cognitive functions Dorsal hippocampus |
| Citations | 7 |
| Key finding | Co-administration of an NPY1R agonist and ketamine enhanced memory consolidation and increased neuronal proliferation in the dorsal hippocampus dentate gyrus, mediated by BDNF and potentially NPY1R-TrkB heteroreceptor complexes. |
Abstract
This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases.