title: Genistein inhibits aggregation of exogenous amyloid-beta₁₋₄₀ and alleviates astrogliosis in the hippocampus of rats.
abstract: We addressed the question of whether injection of Amyloid beta (Aβ)(1-40) in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ(1-40). Genistein is a plant-derived compound with a structure similar to that of the female sex hormone estrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an (Aβ)(1-40) rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ(1-40) positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P<0.0001), CA1 (P=0.03), and CA3 (P=0.002); an increased number of iNOS-expressing cells (P=0.01) and gliosis. Genistein given to rats by gavage 1h before injection of Aβ(1-40) inhibited the formation of Aβ(1-40) positive aggregates in the brain tissue and led to increased number of nNOS(+) (P=0.0001) cells in the hippocampus compared to sham-operated genistein-treated controls. Treatment with genistein also alleviated the extensive astrogliosis that occurred in Aβ(1-40)-injected hippocampus to a level similar to that observed in sham-operated rats. We conclude that the neurons in the DGlb are most sensitive to Aβ(1-40), and a single dose of genistein can ameliorate Aβ(1-40) induced pathology.
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. Maryam.bagheri@liu.se
authors.forename: Maryam
authors.initials: M
authors.lastname: Bagheri
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Roghani
authors.forename: Mohammad-Taghi
authors.initials: MT
authors.lastname: Joghataei
authors.forename: Simin
authors.initials: S
authors.lastname: Mohseni
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D019833:Genistein / Q000494:pharmacology*; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D010446:Peptide Fragments / Q000633:toxicity*; D048789:Phytoestrogens / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D048789:Phytoestrogens; C078592:amyloid beta-protein (1-40); D019833:Genistein