☆ 4.5 Article

Guanosine prevents behavioral alterations in the forced swimming test and hippocampal oxidative damage induced by acute restraint stress

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR (2014)

Journal

PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR

Volume 127, Issue -, Pages 7-14

Publisher

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.pbb.2014.10.002

Keywords

Acute restraint stress; Antidepressant; Antioxidant; Guanosine; Oxidative stress

Funding

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [308723/2013-9]
Rede Instituto Brasileiro de Neurociencias (IBN-Net/CNPq) [01.06.0842-00]
NENASC Project (PRONEX-FAPESC/CNPq) [1262/2012-9]
Coordenacao de Aperfeicoamento de pessoal de nivel superior (CAPES)

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

Guanosine is a guanine-based purine that modulates glutamate uptake and exerts neurotrophic and neuroprotective effects. In a previous study, our group demonstrated that this endogenous nucleoside displays antidepressant-like properties in a predictive animal model. Based on the role of oxidative stress in modulating depressive disorders as well as on the association between the neuroprotective and antioxidant properties of guanosine, here we investigated if its antidepressant-like effect is accompanied by a modulation of hippocampal oxidant/antioxidant parameters. Adult Swiss mice were submitted to an acute restraint stress protocol, which is known to cause behavioral changes that are associated with neuronal oxidative damage. Animals submitted to ARS exhibited an increased immobility time in the forced swimming test (FST) and the administration of guanosine (5 mg/kg, p.o.) or fluoxetine (10 mg/kg, p.o., positive control) before the exposure to stressor prevented this alteration. Moreover, the significantly increased levels of hippocampal malondialdehyde (MDA; an indicator of lipid peroxidation), induced by ARS were not observed in stressed mice treated with guanosine. Although no changes were found in the hippocampal levels of reduced glutathione (GSH), the group submitted to ARS procedure presented enhanced glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) activities and reduced catalase (CAT) activity in the hippocampus. Guanosine was able to prevent the alterations in GPx, GR, CAT activities, and in SOD/CAT activity ratio, but potentiated the increase in SOD activity elicited by ARS. Altogether, the present findings indicate that the observed antidepressant-like effects of guanosine might be related, at least in part, to its capability of modulating antioxidant defenses and mitigating hippocampal oxidative damage induced by ARS. (C) 2014 Elsevier Inc. All rights reserved.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5

Not enough ratings

Secondary Ratings

Novelty

Significance

Scientific rigor

Rate this paper

Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene Nr4a1 in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine

Paola Brivio, Maria Teresa Gallo, Piotr Gruca, Magdalena Lason, Ewa Litwa, Fabio Fumagalli, Mariusz Papp, Francesca Calabrese

Summary: Despite the availability of several antidepressant treatments, they are not effective for all patients. Recently, N-acetylcysteine (NAC) has been explored as a potential adjunctive therapy for psychiatric disorders due to its antioxidant properties. Preclinical studies have shown that NAC can enhance neuroplastic mechanisms and improve resilience, particularly through the modulation of Nr4a1 expression.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)