Hippocampal Volume and Microglia Densities are Altered After Long-term (24 months) Ovariectomy in a Nonhuman Primate Model of Menopause

Loss of circulating ovarian hormones that accompanies menopause may increase the risk of dementia with aging. Inflammation is a key component to many diseases of brain aging, and administering ovarian hormones (estrogen therapy, ET) can quell inflammatory responses. Nonhuman primates are an excellent animal model with which to model menopause, given their similarities to humans. We hypothesized that ovarian hormone loss would increase brain inflammation in the hippocampus, an area relevant for cognitive processes such as learning and memory. We further hypothesized that estrogen therapy (ET) would prevent inflammation in this area. Our study employed the brains from 25 perimenopausal monkeys (age approximately 20). These animals were previously ovariectomized and treated with either placebo (OVX) or Premarin (ET), for durations of either 6 month or 24 months. A separate group of animals were available as intact, cycling controls (INT). Using stereological methods, we assessed brain inflammation by quantifying the numbers of microglia in the hippocampus. Compared to INT, the hippocampus of both 24 month OVX and ET animals was reduced in volume, while microglia densities were increased in both groups. Interestingly, animals that were OVX or ET for only 6 months were not statistically different from INT control animals. Our results suggest that not all forms of ET may be effective at mitigating the consequences of OVX, and that there may be long term neurobiological consequences to OVX which do not manifest in shorter time frames.