Antidepressant-like effects of chronic guanosine in the olfactory bulbectomy mouse model

Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nuc...

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Detalles Bibliográficos
Autores: Almeida, Roberto Farina de, Nonose, Yasmine, Ganzella, Marcelo, Loureiro, Samanta Oliveira, Rocha, Andréia Silva da, Machado, Daniele Guilhermano, Bellaver, Bruna, Fontella, Fernanda Urruth, Leffa, Douglas Teixeira, Pettenuzzo, Letícia Ferreira, Venturin, Gianina Teribele, Greggio, Samuel, Costa, Jaderson Costa da, Zimmer, Eduardo Rigon, Elisabetsky, Elaine, Souza, Diogo Onofre Gomes de
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Brasil
Institución:Universidade Federal do Rio Grande do Sul (UFRGS)
Repositorio:Repositório Institucional da UFRGS
Idioma:inglés
OAI Identifier:oai:www.lume.ufrgs.br:10183/230516
Acceso en línea:http://hdl.handle.net/10183/230516
Access Level:acceso abierto
Palabra clave:Antidepressivos
Guanosina
Bulbo olfatório
Transtorno depressivo maior
Major depressive disorder
Psychopharmacology
Purines (source: MeSH)
Guanosine
Purinergic signaling
Olfactory bulbectomy
Descripción
Sumario:Major depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast-onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging ([18F]FDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.

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