Research ReportGenistein 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 (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 Aβ1-40. 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 Aβ1-40 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 Aβ1-40 inhibited the formation of Aβ1-40 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 Aβ1-40-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 Aβ1-40, and a single dose of genistein can ameliorate Aβ1-40 induced pathology.

► Injection of Aβ1-40 into rat brain caused neuronal degeneration in the hippocampus. ► Aβ1-40 injection increased the expression and number of iNOS expressing cells. ► Severe astrogliosis occurred in the hippocampus of Aβ1-40 injected rats. ► Genistein prevented the formation of Aβ-containing aggregates in the hippocampus. ► Genistein treatment alleviated astrogliosis in the hippocampus.