title: Increased tau phosphorylation and receptor for advanced glycation endproducts (RAGE) in the brain of mice infected with Leishmania amazonensis.
abstract: Leishmaniasis is a parasitosis caused by several species of the genus Leishmania, an obligate intramacrophagic parasite. Although neurologic symptoms have been observed in human cases of leishmaniasis, the manifestation of neurodegenerative processes is poorly studied. The aim of the present work was to investigate if peripheral infection of BALB/c mice with Leishmania amazonensis affects tau phosphorylation and RAGE protein content in the brain, which represent biochemical markers of neurodegenerative processes observed in diseases with a pro-inflammatory component, including Alzheimer's disease and Down syndrome. Four months after a single right hind footpad subcutaneous injection of L. amazonensis, the brain cortex of BALB/c mice was isolated. Western blot analysis indicated an increase in tau phosphorylation (Ser(396)) and RAGE immunocontent in infected animals. Brain tissue TNF-α, IL-1β, and IL-6 levels were not different from control animals; however, increased protein carbonylation, decreased IFN-γ levels and impairment in antioxidant defenses were detected. Systemic antioxidant treatment (NAC 20mg/kg, i.p.) inhibited tau phosphorylation and recovered IFN-γ levels. These data, altogether, indicate an association between impaired redox state, tau phosphorylation and RAGE up-regulation in the brain cortex of animals infected with L. amazonensis. In this context, it is possible that neurologic symptoms associated to chronic leishmaniasis are associated to disruptions in the homeostasis of CNS proteins, such as tau and RAGE, as consequence of oxidative stress. This is the first demonstration of alterations in biochemical parameters of neurodegeneration in an experimental model of Leishmania infection.
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Juciano
authors.initials: J
authors.lastname: Gasparotto
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Mario Roberto
authors.initials: MR
authors.lastname: Senger
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Alice
authors.initials: A
authors.lastname: Kunzler
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Degrossoli
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Salvatore Giovanni
authors.initials: SG
authors.lastname: de Simone
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Rafael Calixto
authors.initials: RC
authors.lastname: Bortolin
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Nauana
authors.initials: N
authors.lastname: Somensi
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carolina Saibro
authors.initials: CS
authors.lastname: Girardi
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Celeste da Silva Freitas
authors.initials: Cda S
authors.lastname: de Souza
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Kátia da Silva
authors.initials: Kda S
authors.lastname: Calabrese
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: José Claudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.affiliation: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360 Rio de Janeiro, RJ, Brazil.
authors.forename: Floriano Paes
authors.initials: FP
authors.lastname: Silva
authors.affiliation: Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: dgelain@yahoo.com.br.
authors.forename: Daniel Pens
authors.initials: DP
authors.lastname: Gelain
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000469:parasitology*; D016207:Cytokines / Q000378:metabolism; D007894:Leishmania mexicana; D007896:Leishmaniasis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015854:Up-Regulation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D016875:tau Proteins
keywords: Leishmaniasis; Neurodegeneration; Oxidative stress; RAGE; Tau phosphorylation