Effect of metformin on the neuronal morphology of frontal cortex and hippocampal regions in lipopolysaccharide induced neuroinflammation in male Wistar rats

Abstract

Background: Neuroinflammation in the frontal cortex and hippocampus is the key contributor in the pathogenesis of neurodegenerative diseases. Lipopolysaccharide (LPS) is a bacterial endotoxin (E-coli phenol extract) used to induce the neuroinflammation in animal models. Our study is aimed to study the protective effect of metformin on the neuronal morphology of the frontal cortex and hippocampal regions in lipopolysaccharide induced neuroinflammation. Methods: This is an animal model study, which utilized the twenty-four male Wistar rats of about 6 weeks old. The rats were divided into 4 groups, which included control, experimental and treatment groups. 170 μg/kg of LPS injection was administered intraperitoneally once a week for the first eight weeks and the treatment groups received metformin, which was administered orally (100 mg and 200 mg/kg body weight/day). Rotarod test was used to confirm the neuronal loss and clinical analysis among the groups. Results: Neuronal loss caused by the exposure to LPS in the dentate gyrus, CA4, CA3, CA2, CA1 (cornu ammonis regions) and frontal cortex, has been improved by the metformin treatment. Among the two doses of metformin, 200 mg/kg body weight exhibited better effect than the 100 mg/kg/body weight. The rotarod test findings suggested that, in the MF treated groups, the number of falls were reduced. Conclusion: The histological analysis and clinical observation by the rotarod test revealed that, metformin attenuated the neuroinflammatory damage, suggesting that it has a neuroprotective role. This study recommends repurposing the usage of metformin as a neuroprotective agent.

Keywords

• Metformin
• Morphological and microscopic findings
• Neuroinflammatory diseases
• Neuroprotective agent