Antidepressant-Like Effects of Chronic Guanosine in the Olfactory Bulbectomy Mouse Model
| Autor: | Roberto Farina Almeida, Yasmine Nonose, Marcelo Ganzella, Samanta Oliveira Loureiro, Andréia Rocha, Daniele Guilhermano Machado, Bruna Bellaver, Fernanda Urruth Fontella, Douglas T. Leffa, Letícia Ferreira Pettenuzzo, Gianina Teribele Venturin, Samuel Greggio, Jaderson Costa da Costa, Eduardo R. Zimmer, Elaine Elisabetsky, Diogo O. Souza |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Bulbo olfatório Psychopharmacology Antidepressivos RC435-571 Guanosine Endogeny Major depressive disorder Pharmacology Hippocampal formation Imipramine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurochemical MeSH) [Purines (source] medicine Transtorno depressivo maior Neuroinflammation olfactory bulbectomy Original Research Psychiatry psychopharmacology purines (source: MeSH) major depressive disorder business.industry Purinergic signaling medicine.disease Guanosina Olfactory bulbectomy guanosine Psychiatry and Mental health 030104 developmental biology chemistry business 030217 neurology & neurosurgery medicine.drug purinergic signaling |
| Zdroj: | Frontiers in Psychiatry Repositório Institucional da UFRGS Universidade Federal do Rio Grande do Sul (UFRGS) instacron:UFRGS Frontiers in Psychiatry, Vol 12 (2021) |
| ISSN: | 1664-0640 |
| DOI: | 10.3389/fpsyt.2021.701408 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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