title: Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10mg/kg) on learning and memory impairments was assessed in intrahippocampal Aβ(1-40)-injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of Aβ-lesioned rats. The Aβ-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of Aβ-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity. These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of short-term spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress.
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Maryam
authors.initials: M
authors.lastname: Bagheri
authors.forename: Mohammad-Taghi
authors.initials: MT
authors.lastname: Joghataei
authors.forename: Simin
authors.initials: S
authors.lastname: Mohseni
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000517:prevention & control*; D016229:Amyloid beta-Peptides; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D004965:Estrogen Antagonists / Q000008:administration & dosage; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D057967:Infusions, Intraventricular; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D011939:Mental Recall / Q000187:drug effects; D008845:Microinjections; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments; D048789:Phytoestrogens / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012153:Retention, Psychology / Q000187:drug effects; D018709:Statistics, Nonparametric; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004965:Estrogen Antagonists; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D048789:Phytoestrogens; D017392:Thiobarbituric Acid Reactive Substances; C078592:amyloid beta-protein (1-40); D000077267:Fulvestrant; D004958:Estradiol; D008315:Malondialdehyde; D019833:Genistein