Time course of response to estradiol replacement in ovariectomized mice: brain apolipoprotein E and synaptophysin transiently increase and glial fibrillary acidic protein is suppressed.

The current study examined the effect of long-term estradiol replacement in ovariectomized mice. Estradiol-17beta (E2) pellets or vehicle pellets were implanted at the time of ovariectomy (OVX) in young adult female mice. Five mice from each group were sacrificed at 5, 14, 28 and 49 days after OVX and pellet replacement. Western blotting of homogenates from somatosensory cortex, hippocampus, olfactory bulb and cerebellum was performed to obtain concentrations of glial fibrillary acidic protein (GFAP), apolipoprotein E (apoE) and synaptophysin (SYN). At 5 days after OVX, GFAP levels were not affected by E2 replacement. In contrast to GFAP, synaptophysin and apoE concentrations were significantly elevated by 15% and 25%, respectively, in the E2-replaced group compared to the vehicle-replaced group at 5 days but by 14 days concentrations were equivalent. Late in the time course of this study, at 49 days, GFAP concentrations were higher in the E2-deprived mice but did not increase in the E2-replaced group. Immunocytochemistry for GFAP confirmed this observation. Of note was that these effects occurred in all four brain regions measured. These observations suggest that estradiol is able to suppress reactive gliosis. In addition, E2 replacement in OVX mice is associated with transiently higher levels of apoE and synaptophysin.