GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions.
Administration, Intranasal
Antidepressive Agents
/ metabolism
Brain-Derived Neurotrophic Factor
/ metabolism
COVID-19
/ metabolism
Depressive Disorder, Major
/ metabolism
Gonadal Steroid Hormones
/ pharmacology
Hippocampus
/ metabolism
Neurogenesis
Neuropeptide Y
/ metabolism
Pandemics
Male
Animals
Rats
Receptor, Galanin, Type 2
/ agonists
Receptors, Neuropeptide Y
/ agonists
depression
galanin
hippocampus
neurogenesis
neuropeptide Y
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
28
11
2022
received:
13
08
2022
accepted:
24
12
2022
pubmed:
5
1
2023
medline:
25
2
2023
entrez:
4
1
2023
Statut:
ppublish
Résumé
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.
Substances chimiques
Antidepressive Agents
0
Brain-Derived Neurotrophic Factor
0
Gonadal Steroid Hormones
0
Neuropeptide Y
0
Receptor, Galanin, Type 2
0
Receptors, Neuropeptide Y
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-474Informations de copyright
© 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.
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