AUTHOR=Almeida Roberto Farina , Nonose Yasmine , Ganzella Marcelo , Loureiro Samanta Oliveira , Rocha Andréia , Machado Daniele Guilhermano , Bellaver Bruna , Fontella Fernanda Urruth , Leffa Douglas T. , Pettenuzzo Letícia Ferreira , Venturin Gianina Teribele , Greggio Samuel , da Costa Jaderson Costa , Zimmer Eduardo R. , Elisabetsky Elaine , Souza Diogo O. TITLE=Antidepressant-Like Effects of Chronic Guanosine in the Olfactory Bulbectomy Mouse Model JOURNAL=Frontiers in Psychiatry VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.701408 DOI=10.3389/fpsyt.2021.701408 ISSN=1664-0640 ABSTRACT=

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.