Spatial Memory Impairment Is Associated with Hippocampal Insulin Signals in Ovariectomized Rats

Estrogen influences memory formation and insulin sensitivity. Meanwhile, glucose utilization directly affects learning and memory, which are modulated by insulin signals. Therefore, this study investigated whether or not the effect of estrogen on memory is associated with the regulatory effect of this hormone on glucose metabolism. The relative expression of estrogen receptor β (ERβ) and glucose transporter type 4 (GLUT4) in the hippocampus of rats were evaluated by western blot. Insulin level was assessed by ELISA and quantitative RT-PCR, and spatial memory was tested by the Morris water maze. Glucose utilization in the hippocampus was measured by 2-NBDG uptake analysis. Results showed that ovariectomy impaired the spatial memory of rats. These impairments are similar as the female rats treated with the ERβ antagonist tamoxifen (TAM). Estrogen blockade by ovariectomy or TAM treatment obviously decreased glucose utilization. This phenomenon was accompanied by decreased insulin level and GLUT4 expression in the hippocampus. The female rats were neutralized with hippocampal insulin with insulin antibody, which also impaired memory and local glucose consumption. These results indicated that estrogen blockade impaired the spatial memory of the female rats. The mechanisms by which estrogen blockade impaired memory partially contributed to the decline in hippocampal insulin signals, which diminished glucose consumption.