Genistein inhibits aggregation of exogenous amyloid-beta1-40 and alleviates astrogliosis in the hippocampus of rats

We addressed the question of whether injection of Amyloid beta (A beta)(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 A beta(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 (A beta)(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 A beta(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 1 h before injection of A beta(1-40) inhibited the formation of A beta(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 A beta(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 A beta(1-40), and a single dose of genistein can ameliorate A beta(1-40) induced pathology. (C) 2011 Elsevier B.V. All rights reserved.