Research Article Neuroimmunomodulation 2020;27:87–96 Evaluation of Brain Cytokines and the Level of Brain-Derived Neurotrophic Factor in an Inflammatory Model of Depression Janine Karina Hideko Alfenas Horita a Maria Carolina Machado da Silva a Carolina Zaniboni Ferrari a Erica Leandro Marciano Vieira b Fabricio A. Moreira a Antônio Carlos Pinheiro de Oliveira a Helton José Reis a a Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; b Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Received: July 2, 2020 Accepted: August 25, 2020 Published online: November 11, 2020 Helton Jose dos Reis Department of Pharmacology, Institute of Biological Sciences Universidade Federal de Minas Gerais Campus Pampulha, Av. Antonio Carlos 6627, Belo Horizonte, MG 31270–901 (Brazil) heltonjr @icb.ufmg.br © 2020 S. Karger AG, Basel karger@karger.com www.karger.com/nim Highlights • LPS induced depressive-like behavior in C57Bl/6 mice. • Dexamethasone failed to prevent the behavioral effects of LPS. • Intraperitoneal injection of LPS increased the levels of various cytokines. • Dexamethasone reduced proinflammatory and increased anti-inflammatory cytokines. • Dexamethasone prevented LPS-induced reduction in brain-derived neurotrophic factor in the hippo- campus. DOI: 10.1159/000511181 Keywords Depression · Inflammation · Lipopolysaccharide · Cytokines · Glucocorticoids Abstract Introduction: Major depressive disorder is considered a global public health problem. Inflammatory processes are likely involved in its pathophysiology, but the underlying mechanisms have remained uncertain. Here, we used the model of systemic lipopolysaccharide (LPS) injection to test the hypothesis that depressive-like behaviors occur along with changes in the levels of cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus (HC), pre- frontal cortex (PFC), and hypothalamus (HT), and can be pre- vented by dexamethasone administration. Methods: Adult C57Bl/6 male mice were first isolated for 10 days, and there- after received an injection of dexamethasone (6 mg/kg, in- traperitoneal [i.p.]), saline followed by LPS (0.83 mg/kg, i.p.), or saline. After 6 h, animals were subjected to the forced- swim test (FST) and open-field tests. Immediately after the behavioral tests, they were euthanized and their brains were collected for the biochemical analyses. Results: LPS in- creased the immobility time and reduced the distance trav- elled in the FST and open-field test, respectively. Dexameth- asone increased the immobility time in saline-treated mice but reduced this behavior in the LPS group. LPS increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and interferon (IFN)-γ in most of the regions evaluated. J.K.H.A. Horita and M.C.M. da Silva contributed equally to this work.