Thymoquinone protects against lipopolysaccharides‐induced neurodegeneration and Alzheimer‐like model in mice.

Abstract Background Chronic neuroinflammation has become a cornerstone in the study of neurodegeneration and Alzheimer’s diseases. Thymoquinone is a known anti‐inflammatory agent with a strong antioxidant activity. This study aimed at evaluating its mechanisms of neuroprotective effect against neurodegeneration, cognitive and synaptic dysfunctions in lipopolysaccharides‐induced Alzheimer‐like model in in mice. Methods Following one‐week acclimatization, thirty‐five Swiss mice were distributed randomly into five groups (n = 7). Group I received vehicle (10mL/kg, p.o.), Group II (LPS) received vehicle (10mL/kg), Group III received TQ (15mg/kg), Group IV received TQ (30mg/kg, p.o) and Group V received donepezil (5mg/kg, p.o.) for seven days. Starting from day 8, sixty‐minutes after treatment with vehicle or TQ or donepezil, animals in groups II‐IV were daily injected with LPS (0.5mg/kg, i.p.) consecutively for seven days. Twenty‐four hours after the treatment on day fourteen of the study, Novel Object Recognition, (NORT), Y‐maze, were used to assess cognitive functions. Tumor necrosis factor‐α (TNF‐α), interlukin‐1β (IL‐1β), acetylcholinesterase (AChE) were assessed using ELISA techniques, microglia, amyloid‐beta, choline acetyltransferase (ChaT), synaptophysin, were quantified using immunohistochemistry, while, gene expression of interlukin‐10 and β‐secretase were measured with quantitative Polymerase Chain Reaction. Cox Golgi staining procedure was performed to evaluate morphology of the pyramidal dendrites. Results LPS significantly impaired performance in the Y‐maze and NORT and induced behavioural abnormalities, compared to control. These were all ameliorated by treatment with TQ (15‐30mg/kg). The TQ also significantly (P<0.05) reduced the concentration of LPS‐induced TNF‐α, IL‐1β, AChE and expressions of amyloid‐beta, microglia and β‐secretase/mRNA in hippocampus and prefrontal cortex. The TQ increased IL‐10/mRNA, ChaT, synaptophysin in hippocampus and PFC. TQ significantly (P<0.05) prevented neurodegeneration of dendrite and neuronal cells in the hippocampus of LPS‐treated mice. Conclusion Our study shows that thymoquinone possesses neuroprotective effect against LPS‐induced neurodegeneration and cognitive impairment by suppressing chronic neuroinflammation, cholinergic disruption, depleted synaptic protein and Aβ accumulation.