title: Oleuropein aglycone and polyphenols from olive mill waste water ameliorate cognitive deficits and neuropathology.
abstract: In TgCRND8 (Tg) mice we checked the dose-response effect of diet supplementation with oleuropein aglycone (OLE) at 12.5 or 0.5 mg kg-1of diet. We also studied the effects of dietary intake of the mix of polyphenols present in olive mill waste water administered at a total dose as high as the highest dose of OLE (50 mg kg-1of diet) previously investigated.
  
  
  
  Four month-old Tg mice were equally divided into four groups and treated for 8 weeks with a modified low fat (5.0%) AIN-76 A diet (10 g day-1per mouse) as such, supplemented with OLE (12.5 or 0.5 mg kg-1of diet) or with a mix of polyphenols (50 mg kg-1of diet) found in olive mill waste water. Behavioural performance was evaluated by the step down inhibitory avoidance and object recognition tests. Neuropathology was analyzed by immunohistochemistry.
  
  
  
  OLE supplementation at 12.5 mg kg-1of diet and the mix of polyphenols was found to improve significantly cognitive functions of Tg mice (P < 0.0001). Aß42 and pE-3Aß plaque area and number were significantly reduced in the cortex by OLE and in the cortex and hippocampus by the mix of polyphenols (P < 0.01, P < 0.001 and P < 0.0001). Similar autophagy induction was found in the brain cortex of differently treated mice.
  
  
  
  Our results extend previous data showing that the effects of OLE on behavioural performance and neuropathology are dose-dependent and not closely related to OLE by itself. In fact, diet supplementation with the same dose of a mix of polyphenols found in olive mill waste water resulted in comparable neuroprotection.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pantano
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Luccarini
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence.
authors.forename: Pamela
authors.initials: P
authors.lastname: Nardiello
authors.affiliation: Department of Agricultural Sciences, Food and Environment, University of Perugia, Via S. Costanzo, 06126, Perugia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Servili
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G. B. Morgagni, 50, 50134, Florence.
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Viale G. Pieraccini, 6, 50139, Florence.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Casamenti
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D057888:Iridoid Glucosides; D039823:Iridoids / Q000302:isolation & purification / Q000627:therapeutic use*; D008822:Mice, Transgenic; D031658:Olea / Q000737:chemistry*; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059808:Polyphenols / Q000302:isolation & purification / Q000627:therapeutic use*; D062065:Wastewater / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D057888:Iridoid Glucosides; D039823:Iridoids; D010446:Peptide Fragments; D059808:Polyphenols; D062065:Wastewater; C075222:amyloid beta-protein (1-42); C002769:oleuropein
keywords: Alzheimer's disease; amyloid plaques; authophagy; memory function; oleuropein aglycone; olive polyphenols