Glucagon‐like peptide‐1 analog improves neuronal and behavioral impairment and promotes neuroprotection in a rat model of aluminum‐induced dementia

Abstract

Abstract Background Alzheimer's disease (AD) is a worldwide severe medical and social burden. Liraglutide (LIR) has neuroprotective effects in preclinical animal models. Aim: To explore the probable neuroprotective impact of Glucagon‐like peptide‐1 (GLP‐1) on rats' behavior and to elucidate its underlying mechanisms. Methods: A total of 24 male albino rats were assigned to control, LIR (300 µg/kg subcutaneously (s.c.)), AD only (100 mg/kg aluminum chloride (AlCl3) orally) and LIR + AD treated groups. Eight radial arm maze was performed. Serum blood glucose, proinflammatory cytokines, oxidative stress markers were measured and hippocampal tissue homogenate neurotransmitters were evaluated. Histopathological and immunofluorescent examinations were performed. Results: LIR prevents the impairment of learning and improves both working memory and reference memory through significant reduction of serum tumor necrosis factor (TNF‐α), interleukin 6 (IL‐6) and interferon‐γ (INF‐γ) and malondialdehyde (MDA) and through the increase of superoxide dismutase (SOD), dopamine, adrenaline, and noradrenaline. LIR also improves hippocampal histological features of ALCL3 administrated rats and decreases the percentage of neuronal loss. Conclusion: LIR normalizes ALCL3‐induced dementia. It improves cognitive dysfunction and ameliorates cerebral damage.

Keywords

• aluminum‐induced dementia
• Alzheimer
• cytokines
• eight radial arm maze
• hippocampus
• LIR