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

journal contribution
posted on 2020-07-01, 00:00 authored by Luiza P Géa, Eduarda D da Rosa, Bruna Panizzutti ParryBruna Panizzutti Parry, Érica Z de Aguiar, L F de Oliveira, Pamela Ferrari, Angelo Piato, Rosane Gomez, Rafael Colombo, Adriane R Rosa
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.

History

Journal

Naunyn-Schmiedeberg's Archives of Pharmacology

Volume

393

Issue

7

Pagination

1303 - 1311

Publisher

Springer

Location

Heidelberg, Germany

ISSN

0028-1298

eISSN

1432-1912

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2020, Springer-Verlag GmbH Germany