Discussion
In summary, brain-targeted LME could exert neuroprotective function via suppressing a series of cascades triggered by Aβ aggregates, thus ameliorating Aβ neurotoxicity and associated abnormalities. Given this, LME may serve as an attractive candidate for AD prevention and treatment, and superiority of brain-targeting delivery is highlighted.
Methods
Mice were assigned to the Sham, Aβ, Aβ + LME and Aβ + lycopene dissolved in olive oil (LOO) groups. ICV Aβ1-42 administration was performed, followed by oral gavage of brain-targeted LME or conventional LOO formulation for 3 weeks. Brain samples were harvested for immunohistochemistry, biochemical assays and western blotting analyses.
Results
Our findings verified Aβ-induced neurotoxicity on neuroinflammation, oxidative stress, apoptosis, Aβ metabolisms and synaptic plasticity. LME supplementation dramatically attenuated astrocytosis and microgliosis, decreased malondialdehyde production and rescued antioxidant capacities, normalized apoptotic parameters and alleviated neuronal loss, inhibited amyloidogenic processing and activated non-amyloidogenic pathway, together with upregulating synaptic protein expressions and restoring synaptic plasticity. Nevertheless, most of these phenomena were not observed for mice treated with LOO, implying that LME showed significantly higher therapeutic efficacy against Aβ injury.