GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions.

Autor: Alvarez-Contino JE; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain., Díaz-Sánchez E; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain.; Grupo Hospitalario Vithas, Vithas Málaga, Málaga, Spain., Mirchandani-Duque M; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain., Sánchez-Pérez JA; Unit of Psychiatry, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Málaga, Spain., Barbancho MA; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain., López-Salas A; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain., García-Casares N; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain., Fuxe K; Department of Neuroscience, Karolinska Institute, Stockholm, Sweden., Borroto-Escuela DO; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain.; Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.; Department of Biomolecular Science, Section of Physiology, University of Urbino, Urbino, Italy., Narváez M; Laboratorio NeuronLab, Instituto de Investigación Biomédica de Málaga, Facultad de Medicina, Universidad de Málaga, Malaga, Spain.; Grupo Hospitalario Vithas, Vithas Málaga, Málaga, Spain.; Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2023 Feb; Vol. 238 (2), pp. 459-474. Date of Electronic Publication: 2023 Jan 04.
DOI: 10.1002/jcp.30944
Abstrakt: Dysregulation of adult hippocampal neurogenesis is linked to major depressive disorder (MDD), with more than 300 million people diagnosed and worsened by the COVID-19 pandemic. Accumulating evidence for neuropeptide Y (NPY) and galanin (GAL) interaction was shown in various limbic system regions at molecular-, cellular-, and behavioral-specific levels. The purpose of the current work was to evaluate the proliferating role of GAL2 receptor (GALR2) and Y1R agonists interaction upon intranasal infusion in the ventral hippocampus. We studied their hippocampal proliferating actions using the proliferating cell nuclear antigen (PCNA) on neuroblasts or stem cells and the expression of the brain-derived neurothrophic factor (BDNF). Moreover, we studied the formation of Y1R-GALR2 heteroreceptor complexes and analyzed morphological changes in hippocampal neuronal cells. Finally, the functional outcome of the NPY and GAL interaction on the ventral hippocampus was evaluated in the forced swimming test. We demonstrated that the intranasal infusion of GALR2 and the Y1R agonists promotes neuroblasts proliferation in the dentate gyrus of the ventral hippocampus and the induction of the neurotrophic factor BDNF. These effects were mediated by the increased formation of Y1R-GALR2 heteroreceptor complexes, which may mediate the neurites outgrowth observed on neuronal hippocampal cells. Importantly, BDNF action was found necessary for the antidepressant-like effects after GALR2 and the Y1R agonists intranasal administration. Our data may suggest the translational development of new heterobivalent agonist pharmacophores acting on Y1R-GALR2 heterocomplexes in the ventral hippocampus for the novel therapy of MDD or depressive-affecting diseases.
(© 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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