TY - JOUR
T1 - Selanylimidazopyridine prevents lipopolysaccharide-induced depressive-like behavior in mice by targeting neurotrophins and inflammatory/oxidative mediators
AU - Domingues, Micaela
AU - Casaril, Angela M.
AU - Birmann, Paloma T.
AU - Lourenço, Darling de A.
AU - Vieira, Beatriz
AU - Begnini, Karine
AU - Lenardão, Eder J.
AU - Collares, Tiago
AU - Seixas, Fabiana K.
AU - Savegnago, Lucielli
N1 - Funding Information:
We are grateful to UFPel and especially to the Programa de Pós Graduação em Biotecnologia (UFPel) for providing support to carry out this work. We would like to thank CNPq, CAPES, and FAPERGS for providing financial support.
Publisher Copyright:
© 2018 Domingues, Casaril, Birmann, Lourenço, Vieira, Begnini, Lenardão, Collares, Seixas and Savegnago.
PY - 2018/7/19
Y1 - 2018/7/19
N2 - 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.
AB - 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.
KW - Depression
KW - Imidazopyridines
KW - Lipopolysaccharide
KW - Major depressive disorder
KW - Mouse models of depressive disorder
KW - Neuroinflammation
KW - NFkB
KW - Selenium
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U2 - 10.3389/fnins.2018.00486
DO - 10.3389/fnins.2018.00486
M3 - Article
C2 - 30072867
AN - SCOPUS:85050355565
SN - 1662-4548
VL - 12
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - JUL
M1 - 486
ER -