Lycopene Treatment Ameliorates Amyloid Plaque Deposition and Memory Impairment in the APP/PS1 Mice

Abstract

Alzheimer’s disease (AD) is a neurodegenerative condition associated with oxidative stress and neuroinflammation. Lycopene has previously been shown to ameliorate neuroinflammation and exert protection against oxidative damage in neuroblastoma cells. The role of this compound in reversing cognitive dysfunction in AD has yet to be determined. The present study investigates the role of lycopene in AD with an in vitro Aβ1-42-induced cell cytotoxicity model as well as the in vivo APP/PS1 mouse model. The activation of Nrf2 signal pathway was assessed using western blot and RT-PCR. MDA, 8-OHdG, ROS, SOD, GHS and GSSG measurements were carried out using the specialized assay kits. The Morris water maze was used to examine qualitative assessment of memory and spatial learning. Immunofluorescence was used to visualize astrocytes and microglia activation as well as brain β-amyloid (Aβ) deposition. The NeuN positive cells were detected by immunofluorescence and western blot. Levels of cerebral cytokines were quantified using RT-PCR. Lycopene ameliorates oxidative damage in the Aβ1-42-triggered cell cytotoxicity model via Nrf2-ARE signal pathway activation, which is regulated by AKT-GSK3β pathway. In addition, lycopene improves the cognitive impairment and reduces the Aβ deposition. Mechanistically, lycopene attenuates neuron loss, decreases chronic inflammation and activates cerebral Nrf2-ARE signaling pathway in APP/PS1 mice. The results suggest that lycopene alleviates oxidative stress via AKT- Nrf2-ARE pathway. And early administration of lycopene improves cognitive deficits by reducing Aβ deposition, neuronal loss and decreasing the degree of chronic inflammation.