Guanosine treatment prevents lipopolysaccharide-induced depressive-like behavior in mice

Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamate...

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Published in:	Journal of psychiatric research Vol. 164; pp. 296 - 303
Main Authors:	dos Santos, Rozielly Aparecida Lemes, de Lima Reis, Silvia Regina, Gibbert, Patrícia Cristiane, de Arruda, Cristina Maria, Doneda, Diego Luiz, de Matos, Yohan Alves Victor, Viola, Giordano Gubert, Rios Santos, Fabrício, de Lima, Eliângela, da Silva Buss, Ziliani, Vandresen-Filho, Samuel
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-08-2023
Subjects:	Animals Behavior, Animal Depression Depression - chemically induced Depression - drug therapy Depression - metabolism Fluoxetine - pharmacology Guanosine - pharmacology Hippocampus - metabolism Indoleamine 2,3-dioxygenase 1 Inflammation Lipopolysaccharides - pharmacology Mice Neuroprotective Agents - pharmacology Oxidative stress Purines Tumor necrosis factor-alpha Tumor Necrosis Factor-alpha - metabolism GUO QA Purines Oxidative stress kyn Tumor necrosis factor-alpha TRP Indoleamine 2,3-dioxygenase 1 Depression Inflammation LPS
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Summary:	Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus. [Display omitted] •Guanosine prevents lipopolysaccharide-induced depressive-like behavior.•Guanosine attenuates lipopolysaccharide-induced hippocampal expression of TNF-α.•Guanosine attenuates lipopolysaccharide-induced hippocampal expression of IDO-1.•Guanosine prevents increased oxidative stress induced by lipopolysaccharide.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3956 1879-1379
DOI:	10.1016/j.jpsychires.2023.06.022