Effects of propentofylline and lipopolysaccharide on sickness behavior, depressive-like behavior, and TNF-alpha plasma levels of rats

• Grant number: 14/25113-5
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2015
• Effective date (End): February 29, 2016
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Thiago Berti Kirsten
• Grantee: Marcella Cristina Galvão
• Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Depression is a mood disorder with high prevalence, being one of the major causes of unemployment and suicide, and requiring long and expensive treatments. Little is known about the etiology and pathophysiology of depression that includes genetic, psychological and pharmacological factors. Immune/inflammatory activations have been accepted as inducers of depression. For example, many depressed patients exhibit a chronic increase in pro-inflammatory cytokines levels, such as tumor necrosis factor alpha (TNF-±). Accordingly, several drugs that interfere with the immune system and its bidirectional modulation with the central nervous system have been tested for the treatment of depression, particularly anti-inflammatory drugs. Propentofylline is a xanthine derivative that presents neuroprotective, anti-oxidants, and anti-inflammatory effects. Thus, the aim of this study is to treat rats with propentofylline in an attempt to prevent/ease the depressive-like effects experimentally induced. Male adult Wistar rats will be used. We will use a model that repeatedly administrates lipopolysaccharide (LPS, Gram-negative bacteria endotoxin) to induce depressive-like effects. Rats will receive propentofylline for five consecutive days. First, we will evaluate if the LPS-induced sickness behavior will cease. For this, we will daily assess the open-field general activity and the body weight of the rats. The depressive-like behavior will be evaluated by the forced swim test. We will also evaluate plasma levels of TNF-±, because it is considered a biomarker of depression.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MORAES, MARCIA M. T.; GALVAO, MARCELLA C.; CABRAL, DANILO; COELHO, CIDELI P.; QUEIROZ-HAZARBASSANOV, NICOLLE; MARTINS, MARIA F. M.; BONDAN, EDUARDO F.; BERNARDI, MARIA M.; KIRSTEN, THIAGO BERTI. Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway. PLoS One, v. 12, n. 1 JAN 5 2017. Web of Science Citations: 12.