title: Lycopene abrogates Aβ(1-42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer's disease.
abstract: BACKGROUND
  Neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). β-Amyloid1-42 (Aβ1-42)-induced learning and memory impairment in rats is believed to be associated with neuronal inflammation.
  
  
  OBJECTIVE
  The present study was designed to investigate the effect of lycopene, a potent antioxidant and anti-inflammatory carotenoid, in intracerebroventricular (i.c.v.) Aβ1-42-induced neuroinflammatory cascade along with learning and memory impairment in rats.
  
  
  METHODS
  I.c.v. Aβ1-42 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 α (TNF-α), interleukin 1β (IL-1β), tumor growth factor β (TGF-β), nuclear factor-κB (NF-κB) and caspase-3 were assessed by enzyme-linked immunosorbent assay analysis.
  
  
  RESULTS
  Lycopene remediated Aβ-induced learning and memory deficits in a dose-dependent manner. Aβ1-42-induced mitochondrial dysfunction along with surge of proinflammatory cytokines TNF-α, TGF-β and IL-1β as well as NF-κB and caspase-3 activity in rat brain was significantly reduced with lycopene treatment.
  
  
  CONCLUSIONS
  The amelioration of Aβ1-42-induced spatial learning and memory impairment by lycopene could be linked, at least in part, to the inhibition of NF-κB activity and the down-regulation of expression of neuroinflammatory cytokines, suggesting that lycopene may be a potential candidate for AD treatment.
authors: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India.
authors: Anand Kamal
authors: AK
authors: Sachdeva
authors: Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, 160 014 India. Electronic address: dr_chopra_k@yahoo.com.
authors: Kanwaljit
authors: K
authors: Chopra
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016229:Amyloid beta-Peptides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001522:Behavior, Animal; D002338:Carotenoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D019587:Dietary Supplements / Q000009:adverse effects; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism; D000077276:Lycopene; D008297:Male; D018782:Maze Learning; D000069077:Memory Consolidation; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010446:Peptide Fragments; D011897:Random Allocation; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D002338:Carotenoids; C505410:Casp3 protein, rat; D053148:Caspase 3; D000077276:Lycopene
keywords: Aβ(1–42); Cognitive impairment; Lycopene; Neuroinflammation; Oxidative stress