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

Géa, Luiza P., da Rosa, Eduardo D., Panizzutti, Bruna S., de Aguiar, Érica Z., de Oliveira, Larissa F., Ferrari, Pamela, Piato, Angelo, Gomez, Rosane, Colombo, Rafael and Rosa, Adriane R. 2020, Reduction of hippocampal IL-6 levels in LPS-injected rats following acute exendin-4 treatment, Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 393, no. 7, pp. 1303-1311, doi: 10.1007/s00210-020-01867-5.

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Title Reduction of hippocampal IL-6 levels in LPS-injected rats following acute exendin-4 treatment
Author(s) Géa, Luiza P.
da Rosa, Eduardo D.
Panizzutti, Bruna S.
de Aguiar, Érica Z.
de Oliveira, Larissa F.
Ferrari, Pamela
Piato, Angelo
Gomez, Rosane
Colombo, Rafael
Rosa, Adriane R.
Journal name Naunyn-Schmiedeberg's Archives of Pharmacology
Volume number 393
Issue number 7
Start page 1303
End page 1311
Total pages 9
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2020-07-01
ISSN 0028-1298
1432-1912
Keyword(s) Brain-derived neurotrophic factor
Glucagon-like peptide 1
Inflammation
Interleukin-6
Lipopolysaccharide
Thiobarbituric acid reactive substances
Summary 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.
Language eng
DOI 10.1007/s00210-020-01867-5
Indigenous content off
Field of Research 1115 Pharmacology and Pharmaceutical Sciences
1116 Medical Physiology
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2020, Springer-Verlag GmbH Germany
Persistent URL http://hdl.handle.net/10536/DRO/DU:30146071

Document type: Journal Article
Collection: Faculty of Health
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