Effects of Sex-Specific Factors on Brain Oxidative Stress

Jessica Busler, PhD
Department of Medicine
Division of Women’s Health
Poster Overview

Oxidative stress, an imbalance between free radicals and antioxidants, can lead to cellular damage and is thought to play a role in several psychiatric disorders. While research in animals and using blood samples has shown that oxidative stress differs in males and females, it is not known how biological sex and circulating sex hormones impact on oxidative stress in the brain in humans.

From two research sites (BWH and Johns Hopkins), 15 women and 12 men, ages 35-64, participated in the study. We measured glutathione (GSH), the primary antioxidant in the brain, in three brain locations and in blood. We also examined circulating sex hormones in women in the BWH sample. We tested for sex differences in GSH and examined the relationship of circulating female sex hormones with GSH.

We found that women had lower levels of GSH in the ventromedial prefrontal cortex than men and that circulating female sex hormones in women (estradiol and estrone) were associated with GSH in the anterior cingulate cortex.

Female sex and female sex hormones are related to markers of increased oxidative stress in the brain. Our findings may inform women’s brain health broadly and contribute to the development of sex-specific interventions in psychiatry.

Scientific Abstract

Oxidative stress is implicated in several psychiatric disorders, but it is unknown whether biological sex and sex hormones impact on oxidative stress in the brain. We tested these relationships with concentrations of glutathione (GSH), the primary brain antioxidant.

At BWH, 10 women and 5 men participated, ages 37-58 (M=46.93, SD=7.19). At JHMI, 5 women and 7 men participated, ages 35-64 (M=47.83, SD=9.21). MR spectroscopy was used to assess GSH in the anterior cingulate (ACC), ventromedial prefrontal (VMPFC), and dorsolateral prefrontal cortices (DLPFC). Peripheral GSH was assayed at both sites and circulating sex hormones at BWH only. We conducted a z-score meta-analysis to test biological sex differences and regression analyses to test sex hormones in women as predictors of GSH, controlling for age.

We found that women display lower levels of VMPFC GSH than men (z=-2.10, p=0.04). For sex hormones analyses, we observed that estradiol and estrone were significantly associated with ACC GSH (b=-.82, p=0.01; b=-.74, p=0.02). No other significant effects were observed.

Female sex and sex hormones are related to oxidative stress markers in the brain, particularly in the VMPFC and ACC, respectively. Our findings may inform women’s health broadly and contribute to development of sex-specific antioxidant/estrogenic interventions in psychiatry.

Clinical Implications
Female sex and female sex hormones are related to markers of increased oxidative stress in the brain. Our findings may inform women’s brain health broadly and contribute to the development of sex-specific interventions in psychiatry.
Research Areas
Authors
Jessica N. Busler, Sarah Rose Slate, Eduardo Coello, Vicky Liao, Alexander P. Lin, & Pamela B. Mahon
Principal Investigator
Jessica N. Busler

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