Abstract Title

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

Abstract

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.

Modified Abstract

Loss of circulating ovarian hormones that accompanies menopause may increase the risk of dementia with aging, and estrogen therapy (ET) may prevent these changes. We had access to brains from 25 perimenopausal monkeys. Animals had been ovariectomized and treated with either placebo (OVX) or Premarin (ET) for 6 month or 24 month durations. Intact, cycling controls (INT) were available. Inflammation was assessed by quantifying 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. Animals that were OVX or ET for 6 months were not different from INT animals. Our results suggest that not all forms of ET may be effective at mitigating the consequences of OVX.

Research Category

Biomedical Sciences

Primary Author's Major

Biology

Mentor #1 Information

Gregory Tinkler, Ph.D.

Presentation Format

Video

Start Date

5-4-2018 1:00 PM

Research Area

Endocrine System | Hormones, Hormone Substitutes, and Hormone Antagonists | Nervous System | Nervous System Diseases | Neurosciences

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Apr 5th, 1:00 PM

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.