Rationale and objectives
Stress-induced alterations in oxidative and inflammatory parameters have been implicated in the pathophysiology of mood disorders. Based on the antioxidant and anti-inflammatory properties of the selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole (CMI), we assessed its ability to reverse depression-like behavioral alterations, neuroinflammation, and oxidative imbalance induced by acute restraint stress.
Mice submitted to restraint for 240 min received CMI (1 or 10 mg/kg, orally) 10 min after the end of the stress induction. Behavioral and biochemical tests were carried out after further 30 min.
Restraint-induced depression-like behavior in the tail suspension test (TST), splash test, and new object exploration test was reversed by CMI. None of the treatments evoked locomotor alteration. In addition, CMI abrogated restraint-induced increases in plasma levels of corticosterone and in markers of oxidative stress and impaired superoxide dismutase and catalase activity in the prefrontal cortex (PFC) and hippocampus (HC). CMI also blocked stress-induced downregulation of mRNA levels of glucocorticoid receptor and brain-derived neurotrophic factor and upregulation of nuclear factor kappa B, inducible nitric oxide synthase, tumor necrosis alpha, indoelamine-2,3-dioxygenase, and glycogen synthase kinase 3 beta in PFC and HC.
These preclinical results indicate that administration of selenium-containing compounds might help to treat depression associated with inflammation and oxidative stress.
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The authors are grateful to UFPel and especially to the Biotechnology Graduate Program (UFPel) for providing support to carry out this work. CNPq is also acknowledged for the fellowship to LS, EL, FS, TC, and CWN.
AMC and MD performed the experiments and the analysis of data and wrote the manuscript. SRB, DAL, and MS performed the experiments. AMC, MD, and LS designed the project. NBP and EJL synthesized the compound CMI. TC, FKS, LS, and CWN supervised the experiments. RD revised the scientific content of the manuscript and provided valuable intellectual insights. All authors critically reviewed the content and approved the final version for publication.
Role of funding source
This study received financial support and scholarships from the Brazilian agencies CNPq, CAPES, and FAPERGS (PRONEM 16/2551-0000240-1, PqG 17/2551-00011046-9, and FAPERGS/CAPES 04/2018 - DOCFIX 18/2551-0000511-8).
The studies were performed in accordance with protocols approved by the Committee on the Care and Use of Experimental Animal Resources at the Federal University of Pelotas, Brazil (4034-2017).
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Casaril, A.M., Domingues, M., Bampi, S.R. et al. The selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole reverses depressive-like behavior induced by acute restraint stress in mice: modulation of oxido-nitrosative stress and inflammatory pathway. Psychopharmacology 236, 2867–2880 (2019). https://doi.org/10.1007/s00213-018-5151-x
- Acute restraint stress
- Oxidative stress