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