Reduction of hippocampal IL-6 levels in LPS-injected rats following acute exendin-4 treatment.

Autor: Géa LP; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil.; Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., da Rosa ED; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil.; Programa de Pós-gradução em Ciências Biológicas: Bioquímica, UFRGS, Porto Alegre, RS, Brazil., Panizzutti BS; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil.; Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, UFRGS, Porto Alegre, RS, Brazil., de Aguiar ÉZ; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil., de Oliveira LF; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil., Ferrari P; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil., Piato A; Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Gomez R; Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil., Colombo R; Laboratório de Farmacologia e Fisiologia, Universidade de Caxias do Sul (UCS), Caixas do Sul, RS, Brazil., Rosa AR; Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-007, Brazil. adrianerrosa@gmail.com.; Programa de Pós-graduação em Ciências Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. adrianerrosa@gmail.com.; Programa de Pós-graduação em Psiquiatria e Ciências do Comportamento, UFRGS, Porto Alegre, RS, Brazil. adrianerrosa@gmail.com.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2020 Jul; Vol. 393 (7), pp. 1303-1311. Date of Electronic Publication: 2020 May 03.
DOI: 10.1007/s00210-020-01867-5
Abstrakt: Preclinical evidence on the role of glucagon-like peptide-1 receptor (GLP-1r) agonists in the brain led to an increased interest in repurposing these compounds as a therapy for central nervous system (CNS) disorders and associated comorbidities. We aimed to investigate the neuroprotective effects of acute treatment with exendin (EX)-4, a GLP-1r agonist, in an animal model of inflammation. We evaluated the effect of different doses of EX-4 on inflammatory, neurotrophic, and oxidative stress parameters in the hippocampus and serum of lipopolysaccharide (LPS)-injected animals. Male Wistar rats were injected with LPS (0.25 mg/kg i.p.) and treated with different doses of EX-4 (0.1, 0.3, or 0.5 μg/kg i.p.). Sickness behavior was assessed by locomotor activity and body weight, and depressive-like behavior was also evaluated using forced swim test (FST). Brain-derived neurotrophic factor (BDNF), thiobarbituric acid reactive species (TBARS), and interleukin (IL)-6 were quantified in the serum and hippocampus. Glycemia was also analyzed pre- and post-EX-4 treatment. LPS groups exhibited decreased frequency of crossing and reduced body weight (p < 0.001), while alterations on FST were not observed. The higher dose of EX-4 reduced IL-6 in the hippocampus of LPS-injected animals (p = 0.018), and EX-4 per se reduced TBARS serum levels with a modest antioxidant effect in the LPS groups (p ≤ 0.005). BDNF hippocampal levels seemed to be increased in the LPS+EX-4 0.5 group compared with LPS+Saline (p > 0.05). Our study provides evidence on acute anti-inflammatory effects of EX-4 in the hippocampus of rats injected with LPS, contributing to future studies on repurposing compounds with potential neuroprotective properties.
Databáze: MEDLINE
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