Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer’s disease: an exploration of underlying mechanisms

Zahra Kiasalari Reineh | Rana Heydarifard | Mohsen Khalili | Tourandokht Baluchnejadmojarad | Mohsen Balhalili | Tourandokht Baluchnejadmojarad | Mohsen | Baluchnejadmojarad | Tourandokht | Y Afshin-Majd | Siamak Sanaierad | Ashkan | Zahedi | Elham | Roghani | Mehrdad

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URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=43167
Date :  2016/12/01
Publish in :    Psychopharmacology

Link :  https://www.ncbi.nlm.nih.gov/pubmed/28303372
Keywords :Ellagic acid . Alzheimer’s disease . Amyloid beta. Learning and memory . Oxidative stress . Neuroinflammation

Abstract :

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Rationale 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 Aβ25-35 and 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, 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.