# The role of stress exposure on estradiol-induced changes in neuroinflammation and cognition

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $743,577

## Abstract

Abstract
The number of people suffering from age-related cognitive decline is growing at an unprecedented rate as the
human lifespan increases. In addition, exposure to social adversity and other stressors increases risk for
cognitive deficits which may be exacerbated in aging. Because women are at greater risk for developing
cognitive impairment compared to men, a potential role for estradiol is implicated. However, findings from
studies assessing the effects of estradiol on cognition are equivocal. Consequently, there is a need to
understand whether adverse experiential factors may impact estradiol efficacy that would account for the
variance in the effects of estradiol on cognitive aging in females. One mechanism by which stress exposure
and estradiol both impact cognition and memory is modulation of neuro-inflammatory processes that alter
neurotransmitter release and synthesis and are associated with unhealthy aging. Despite observations that
chronic stress exposure increases vulnerability to cognitive decline, it is not clear whether stress induced
alterations in estradiol’s efficacy in modulating neuroinflammation and cognitive behavior. To fill this gap in
knowledge, the proposed studies will leverage a well characterized non-human primate model of psychosocial
stress to test the overarching hypothesis that low social status produces cognitive deficits in female rhesus
monkeys and neuroinflammation in the brain that are exacerbated by estradiol. Using social group
rearrangements and estradiol manipulations, we will test the effects of social status and age on
neuroinflammation by using PET neuroimaging to site-specifically quantify microglial activation in the brain, as
well as measure concentrations of pro-inflammatory signals in cerebral spinal fluid. We will also determine the
effects of chronic social status and age on cognitive flexibility and memory capacity, and determine the extent
to which neuroinflammation account for variance in executive function assessed. Finally, we will determine the
causal effects of social status on estradiol’s ability to modulate neuroinflammation and cognition. At its
conclusion, the proposed studies will extend upon our previous work by following the same individuals across
experimentally determined changes in their social status to generate insight into both the causal effects of
social status on estradiol’s ability to influence cognitive behavior and brain region-specific markers of
neuroinflammation and their plasticity with changes in the social environment. By assessing and integrating the
physiological, neurobiological, and behavioral data collected as part of the proposed studies, we will be able to
identify a novel mechanism underlying risk for aging-related health disparities in the female brain.

## Key facts

- **NIH application ID:** 10850791
- **Project number:** 5R01AG078248-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** MARIA C ALVARADO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $743,577
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850791

## Citation

> US National Institutes of Health, RePORTER application 10850791, The role of stress exposure on estradiol-induced changes in neuroinflammation and cognition (5R01AG078248-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10850791. Licensed CC0.

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