Selanylimidazopyridine Prevents Lipopolysaccharide-Induced Depressive-Like Behavior in Mice by Targeting Neurotrophins and Inflammatory/Oxidative Mediators

• Published in: Frontiers in neuroscience Vol. 12; p. 486
• Main Authors: Domingues, Micaela, Casaril, Angela M, Birmann, Paloma T, Lourenço, Darling de A, Vieira, Beatriz, Begnini, Karine, Lenardão, Eder J, Collares, Tiago, Seixas, Fabiana K, Savegnago, Lucielli
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 19.07.2018; Frontiers Media S.A
• Subjects: Animals; Antidepressants; Antioxidants; Behavior; Brain-derived neurotrophic factor; Canola; Chronic fatigue syndrome; Cytokines; depression; Diabetes; Drug dosages; Hippocampus; imidazopyridines; Inflammation; Lipid peroxidation; lipopolysaccharide; Lipopolysaccharides; major depressive disorder; Mental depression; Neuroprotection; Neuroscience; Neurosciences; Neurotrophic factors; NF-κB protein; NFkB; Oxidative stress; Prefrontal cortex; Psychotropic drugs; Pyridines; Reactive oxygen species; selenium; Selenium compounds; Brazil; major depressive disorder; selenium; neuroinflammation; NFkB; depression; lipopolysaccharide; mouse models of depressive disorder; imidazopyridines
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2018.00486

Inasmuch, as the major depressive disorder (MDD) has been characterized as a heterogeneous disease as the inflammatory processes, neurotrophic factors' dysfunction and oxidative/nitrosative stress are believed to play a vital role in its establishment. Organoselenium compounds stand out due to their antioxidant, anti-inflammatory, neuroprotective, and antidepressant effects. In this sense, the present study investigated the effect of 3-((4-methoxyphenyl)selanyl)-2-phenylimidazo[1,2-a]pyridine (MPI; 20 and 50 mg/kg, intragastrically) pretreatment [30 min prior lipopolysaccharide (LPS) challenge (0.83 mg/kg)] on acute LPS induced depressive-like behavior, neuroinflammation, and oxidative stress. MPI was able to prevent the increased immobility time induced by LPS on the forced swimming test (FST), the increase in pro-inflammatory cytokines' expression in the hippocampus (HC) of mice after LPS challenge via NFkB downregulation, and the increase of the reactive oxygen species generation and lipid peroxidation in the prefrontal cortex and HC of mice. It was observed that at the doses tested, MPI protected against reducing levels of BDNF in the cortex and HC of mice challenged with LPS. These observations suggest that the antidepressant-like effect of MPI depends on its capacity to modulate the inflammatory, antioxidant, and neurotrophic systems.