title: Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer's disease: an exploration of underlying mechanisms.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a neurodegenerative disorder with irreversible loss of intellectual abilities. Current therapies for AD are still insufficient.
  
  
  OBJECTIVE
  In this study, the effect of ellagic acid on learning and memory deficits was evaluated in intrahippocampal amyloid beta (Aβ25-35)-microinjected rats and its modes of action were also explored.
  
  
  METHODS
  AD rat model was induced by bilateral intrahippocampal microinjection of Aβ25-35and ellagic acid was daily administered (10, 50, and 100 mg/kg), and learning, recognition memory, and spatial memory were evaluated in addition to histochemical assessment, oxidative stress, cholinesterases activity, and level of nuclear factor-kappaB (NF-κB), Toll-like receptor 4 (TLR4), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2).
  
  
  RESULTS
  The amyloid beta-microinjected rats showed a lower discrimination ratio in novel object and alternation score in Y maze tasks and exhibited an impairment of retention and recall capability in passive avoidance paradigm and higher working and reference memory errors in radial arm maze (RAM). In addition, amyloid beta group showed a lower number of Nissl-stained neurons in CA1 area in addition to enhanced oxidative stress, higher activity of cholinesterases, greater level of NF-κB and TLR4, and lower level of nuclear/cytoplasmic ratio for Nrf2 and ellagic acid at a dose of 100 mg/kg significantly prevented most of these abnormal alterations.
  
  
  CONCLUSIONS
  Ellagic acid pretreatment of intrahippocampal amyloid beta-microinjected rats could dose-dependently improve learning and memory deficits via neuronal protection and at molecular level through mitigation of oxidative stress and acetylcholinesterase (AChE) activity and modulation of NF-κB/Nrf2/TLR4 signaling pathway.
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Kiasalari
authors.affiliation: School of Medicine, Shahed University, Tehran, Iran.
authors.forename: Rana
authors.initials: R
authors.lastname: Heydarifard
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khalili
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran.
authors.forename: Siamak
authors.initials: S
authors.lastname: Afshin-Majd
authors.affiliation: Department of Physiology, School of Medicine, Iran University of Medical sciences, Tehran, Iran.
authors.forename: Tourandokht
authors.initials: T
authors.lastname: Baluchnejadmojarad
authors.affiliation: School of Medicine, Shahed University, Tehran, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Zahedi
authors.affiliation: School of Medicine, Shahed University, Tehran, Iran.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Sanaierad
authors.affiliation: Neurophysiology Research Center, Shahed University, Tehran, Iran. mehjour@yahoo.com.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D004610:Ellagic Acid
keywords: Alzheimer’s disease; Amyloid beta; Ellagic acid; Learning and memory; Neuroinflammation; Oxidative stress