期刊
JOURNAL OF PSYCHIATRIC RESEARCH
卷 164, 期 -, 页码 296-303出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jpsychires.2023.06.022
关键词
Purines; Depression; Inflammation; Indoleamine 2; 3-dioxygenase 1; Tumor necrosis factor-alpha; Oxidative stress
类别
This study investigated the antidepressant-like effects and mechanisms of action of guanosine in a mouse model of lipopolysaccharide (LPS)-induced depression. The results showed that guanosine could prevent LPS-induced depressive-like behaviors by preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.
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-& alpha; (TNF-& alpha;), 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-& alpha; 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-& alpha; in the hippocampus.
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