Lycopene abrogates Aβ(1-42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer's disease

Background: Neuro inflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). beta-Amyloid(1-42) (A beta(1-42))-induced learning and memory impairment in rats is believed to be associated with neuronal inflammation. Objectives: The present study was designed to investigate the effect of lycopene, a potent antioxidant and anti-inflammatory carotenoid, in intracerebroventricular (ICV) A beta(1-42)-induced neuroinflammatory cascade along with learning and memory impairment in rats. Material and methods: ICV A beta(1-42) was injected bilaterally followed by treatment with lycopene or rivastigmine for 14 days. Morris water maze and elevated plus maze tests were used to assess the memory function. Rats were sacrificed and brains harvested to evaluate various biochemical parameters and mitochondrial complex activities in postmitochondrial supernatant fractions of cerebral cortex and hippocampus of rat brains. The levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), tumor growth factor beta (TGF-beta), nuclear factor-kappa B (NF-kappa B) and caspase-3 were assessed by enzyme-linked immunosorbent assay analysis. Results: Lycopene remediated A beta-induced learning and memory deficits in a dose-dependent manner. A beta(1-42)-induced mitochondrial dysfunction along with surge of proinflammatory cytokines TNF-alpha, TGF-beta and IL-1 beta as well as NF-kappa B and caspase-3 activity in rat brain was significantly reduced with lycopene treatment. Conclusion: The amelioration of A beta(1-42)-induced spatial learning and memory impairment by lycopene could be linked, at least in part, to the inhibition of NF-kappa B activity and the down-regulation of expression of neuroinflammatory cytokines, suggesting that lycopene may be a potential candidate for AD treatment. (C) 2015 Elsevier Inc. All rights reserved.