Genistein is effective against amyloid-β toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a r...Genistein is effective against amyloid-β toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a role in the prevention of Alzheimer＇s disease. A rat model of Alzheimer＇s disease was established by intraperitoneal injection of D-galactose and intracerebral injection of amyloid-β peptide （25-35）. In the genistein treatment groups, a 7-day pretreatment with genistein （10, 30, 90 mg/kg） was given prior to establishing Alzheimer＇s disease model, for 49 consecutive days. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated a reduction in apoptosis in the hippocampus of rats treated with genistein. Western blot analysis showed that expression levels of capase-3, Bax and cytochrome c were decreased compared with the model group. Furthermore, immunohistochemical staining revealed reductions in cytochrome c and Bax immunoreactivity in these rats. Morris water maze revealed a substantial shortening of escape latency by genistein in Alzheimer＇s disease rats. These findings suggest that genistein decreases neuronal loss in the hippocampus, and improves learning and memory ability. The neuroprotective effects of genistein are associated with the inhibition of the mitochondrial apoptotic pathway, as shown by its ability to reduce levels of caspase-3, Bax and cytochrome c.展开更多
基金supported by the National Natural Science Foundation of China,No.81202941the Key Project Foundation of Oversea Visiting and Research for the Excellent Young and Middle-aged Faculties in Universities of Anhui Province in China,No.gxfx ZD2016119the Key Project Foundation of Natural Science Research in Universities of Anhui Province in China,No.KJ2016A406
文摘Genistein is effective against amyloid-β toxicity, but the underlying mechanisms are unclear. We hypothesized that genistein may protect neurons by inhibiting the mitochondrial apoptotic pathway, and thereby play a role in the prevention of Alzheimer＇s disease. A rat model of Alzheimer＇s disease was established by intraperitoneal injection of D-galactose and intracerebral injection of amyloid-β peptide （25-35）. In the genistein treatment groups, a 7-day pretreatment with genistein （10, 30, 90 mg/kg） was given prior to establishing Alzheimer＇s disease model, for 49 consecutive days. Terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated a reduction in apoptosis in the hippocampus of rats treated with genistein. Western blot analysis showed that expression levels of capase-3, Bax and cytochrome c were decreased compared with the model group. Furthermore, immunohistochemical staining revealed reductions in cytochrome c and Bax immunoreactivity in these rats. Morris water maze revealed a substantial shortening of escape latency by genistein in Alzheimer＇s disease rats. These findings suggest that genistein decreases neuronal loss in the hippocampus, and improves learning and memory ability. The neuroprotective effects of genistein are associated with the inhibition of the mitochondrial apoptotic pathway, as shown by its ability to reduce levels of caspase-3, Bax and cytochrome c.
