title: Propentofylline Prevents Sickness Behavior and Depressive-Like Behavior Induced by Lipopolysaccharide in Rats via Neuroinflammatory Pathway.
abstract: Recent studies have demonstrated the intimate relationship between depression and immune disturbances. Aware of the efficacy limits of existing antidepressant drugs and the potential anti-inflammatory properties of propentofylline, we sought to evaluate the use of propentofylline as a depression treatment. We used a rat model of depression induced by repetitive lipopolysaccharide (LPS) administrations. We have studied sickness behavior, by assessing daily body weight, open field behavior, and TNF-α plasmatic levels. Anxiety-like behavior (light-dark test), depressive-like behavior (forced swim test), plasmatic levels of the brain-derived neurotrophic factor (BDNF, depression biomarker), and central glial fibrillary acidic protein (GFAP) expression (an astrocyte biomarker) were also evaluated. LPS induced body weight loss, open field behavior impairments (decreased locomotion and rearing, and increased immobility), and increased TNF-α levels in rats, compared with control group. Thus, LPS induced sickness behavior. LPS also increased the immobility and reduced climbing in the forced swim test, when compared with the control group, i.e., LPS induced depressive-like behavior in rats. Propentofylline prevented sickness behavior after four days of consecutive treatment, as well as prevented the depressive-like behavior after five days of consecutive treatments. Propentofylline also prevented the increase in GFAP expression induced by LPS. Neither LPS nor propentofylline has influenced the anxiety and BDNF levels of rats. In conclusion, repetitive LPS administrations induced sickness behavior and depressive-like behavior in rats. Propentofylline prevented both sickness behavior and depressive-like behavior via neuroinflammatory pathway. The present findings may contribute to a better understanding and treatment of depression and associated diseases.
authors.affiliation: Environmental and Experimental Pathology, Paulista University, Sao Paulo, Brazil.
authors.forename: Márcia M T
authors.initials: MM
authors.lastname: Moraes
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of São Paulo, Sao Paulo, Brazil.
authors.forename: Marcella C
authors.initials: MC
authors.lastname: Galvão
authors.affiliation: Environmental and Experimental Pathology, Paulista University, Sao Paulo, Brazil.
authors.forename: Danilo
authors.initials: D
authors.lastname: Cabral
authors.affiliation: Graduate Program of Animal Medicine and Welfare, University of Santo Amaro, Sao Paulo, Brazil.
authors.forename: Cideli P
authors.initials: CP
authors.lastname: Coelho
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of São Paulo, Sao Paulo, Brazil.
authors.forename: Nicolle
authors.initials: N
authors.lastname: Queiroz-Hazarbassanov
authors.affiliation: Environmental and Experimental Pathology, Paulista University, Sao Paulo, Brazil.
authors.forename: Maria F M
authors.initials: MF
authors.lastname: Martins
authors.affiliation: Environmental and Experimental Pathology, Paulista University, Sao Paulo, Brazil.
authors.forename: Eduardo F
authors.initials: EF
authors.lastname: Bondan
authors.affiliation: Environmental and Experimental Pathology, Paulista University, Sao Paulo, Brazil.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Bernardi
authors.affiliation: Environmental and Experimental Pathology, Paulista University, Sao Paulo, Brazil.|Department of Pathology, School of Veterinary Medicine, University of São Paulo, Sao Paulo, Brazil.
authors.forename: Thiago Berti
authors.initials: TB
authors.lastname: Kirsten
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D055809:Illness Behavior / Q000187:drug effects; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D010784:Photomicrography; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014970:Xanthines / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; C032114:propentofylline