Neuroprotective Effect of Lycopene on the Prefrontal Cortex of a Lipopolysaccharide-Induced Rat Model of Alzheimer’s Disease

Abstract

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is characterized by a progressive decline in memory, thinking, and behavior. Given the absence of a definitive cure for AD, there is an urgent need for accessible therapeutic strategies that can halt or slow its progression. Aim: To investigate the neuroprotective effect of lycopene on the prefrontal cortex in a lipopolysaccharide (LPS)-induced rat model of Alzheimer’s disease (AD) by assessing neurobehavioral changes and histoarchitectural alterations. Methodology: Fifty adult male Wistar rats (195-220g) were randomly assigned to five groups (n=10). Group A (Control) received water and non-pellitized feed ad libitum. Group B (LPS) received 15mg/kg LPS intraperitoneally (IP) for 20 days. Group C (Curative) received LPS for 10 days, followed by 15mg/kg lycopene orally for 10 days. Group D (Preventive) received lycopene for 10 days, followed by LPS for 10 days. Group E (Lycopene) received 15mg/kg lycopene orally for 20 days. Neurobehavioral assessments (Y-maze for spatial working memory and Elevated Plus Maze for anxiety/exploration) were conducted. Prefrontal cortex tissues were processed for Haematoxylin and Eosin (H & E) and Bielschowsky’s silver staining for histological evaluation. Results: LPS administration (Group B) caused significant cognitive deficits, evidenced by decreased spontaneous alternation (P < 0.0001) and increased same-arm returns (P < 0.0001) in the Y-maze. In the Elevated Plus Maze, LPS-treated rats showed significantly fewer open arm entries (P < 0.0001) and more closed arm entries (P < 0.0001), indicating heightened anxiety. Histologically, the prefrontal cortex of LPS-treated rats exhibited pyknotic pyramidal neurons and loosely arranged nerve fibers. Lycopene treatment, in both curative and preventive regimens (Groups C and D), significantly ameliorated these behavioral deficits and preserved neuronal architecture. Conclusion: Lycopene demonstrated significant neuroprotective effects against LPS-induced prefrontal cortex damage in a rat model of AD. These benefits are likely mediated through its potent antioxidant properties. This study supports the potential of lycopene as a therapeutic nutritional supplement to combat the progression of Alzheimer's disease.