Viviane de Sousa Tomaz1, Adriano José Maia Chaves Filho1, Rafaela Carneiro Cordeiro1, Paloma Marinho Jucá1, Michelle Verde Ramo Soares1, Poliana Noronha Barroso1, Larissa Maria Frota Cristino1, Wei Jiang2, Antônio Lúcio Teixeira3, David F de Lucena1, Danielle S Macedo4. 1. Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil. 2. Department of Microbiology and Immunology, and Department of Medicine, Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina, USA. 3. Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, Texas, USA; Santa Casa BH Ensino e Pesquisa, Belo Horizonte, Minas Gerais, Brazil. 4. Neuropharmacology Laboratory, Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, SP, Brazil.. Electronic address: danielle.macedo@ufc.br.
Abstract
BACKGROUND: Depressed patients present increased plasma levels of lipopolysaccharide (LPS) and neuroinflammatory alterations. Here, we determined the neuroimmune effects of different classes of ADs by using the LPS inflammatory model of depression. METHODS: Male rats received amitriptyline (AMI) a tricyclic, S-citalopram (ESC) a selective serotonin reuptake inhibitor, tranylcypromine (TCP) a monoamine oxidase inhibitor, vortioxetine (VORT) a multimodal AD or saline for ten days. One-hour after the last AD administration, rats were exposed to LPS 0.83 mg/kg or saline and 24 h later were tested for depressive-like behavior. Plasma corticosterone, brain levels of nitrite, pro- and anti-inflammatory cytokines, phospho-cAMP Response Element-Binding Protein (CREB) and nuclear factor (NF)-kB p 65 were determined. RESULTS: LPS induced despair-like, impaired motivation/self-care behavior and caused anhedonia. All ADs prevented LPS-induced despair-like behavior, but only VORT rescued impaired self-care behavior. All ADs prevented LPS-induced increase in brain pro-inflammatory cytokines [interleukin (IL)-1β and IL-6] and T-helper 1 cytokines [tumor necrosis factor (TNF)-α and interferon-γ]. VORT increased striatal and hypothalamic IL-4 levels. All ADs prevented LPS-induced neuroendocrine alterations represented by increased levels of hypothalamic nitrite and plasma corticosterone response. VORT and ESC prevented LPS-induced increase in NF-kBp65 hippocampal expression, while ESC, TCP and VORT, but not IMI, prevented the alterations in phospho-CREB expression. LIMITATIONS: LPS model helps to understand depression in a subset of depressed patients with immune activation. The levels of neurotransmitters were not determined. CONCLUSION: This study provides new evidence for the immunomodulatory effects of ADs, and shows a possible superior anti-inflammatory profile of TCP and VORT.
BACKGROUND:Depressedpatients present increased plasma levels of lipopolysaccharide (LPS) and neuroinflammatory alterations. Here, we determined the neuroimmune effects of different classes of ADs by using the LPS inflammatory model of depression. METHODS: Male rats received amitriptyline (AMI) a tricyclic, S-citalopram (ESC) a selective serotonin reuptake inhibitor, tranylcypromine (TCP) a monoamine oxidase inhibitor, vortioxetine (VORT) a multimodal AD or saline for ten days. One-hour after the last AD administration, rats were exposed to LPS 0.83 mg/kg or saline and 24 h later were tested for depressive-like behavior. Plasma corticosterone, brain levels of nitrite, pro- and anti-inflammatory cytokines, phospho-cAMP Response Element-Binding Protein (CREB) and nuclear factor (NF)-kB p 65 were determined. RESULTS:LPS induced despair-like, impaired motivation/self-care behavior and caused anhedonia. All ADs prevented LPS-induced despair-like behavior, but only VORT rescued impaired self-care behavior. All ADs prevented LPS-induced increase in brain pro-inflammatory cytokines [interleukin (IL)-1β and IL-6] and T-helper 1 cytokines [tumor necrosis factor (TNF)-α and interferon-γ]. VORT increased striatal and hypothalamic IL-4 levels. All ADs prevented LPS-induced neuroendocrine alterations represented by increased levels of hypothalamic nitrite and plasma corticosterone response. VORT and ESC prevented LPS-induced increase in NF-kBp65 hippocampal expression, while ESC, TCP and VORT, but not IMI, prevented the alterations in phospho-CREB expression. LIMITATIONS: LPS model helps to understand depression in a subset of depressedpatients with immune activation. The levels of neurotransmitters were not determined. CONCLUSION: This study provides new evidence for the immunomodulatory effects of ADs, and shows a possible superior anti-inflammatory profile of TCP and VORT.
Authors: Jesús Aranda; María Del Mar Fernández-Arjona; Francisco Alén; Patricia Rivera; Leticia Rubio; Inés Smith-Fernández; Francisco Javier Pavón; Antonia Serrano; Pedro J Serrano-Castro; Fernando Rodríguez de Fonseca; Juan Suárez Journal: Brain Struct Funct Date: 2021-07-08 Impact factor: 3.270