Skip to Content

Institute for Cardiovascular Disease Research

Project 2: Brain and Stress

Stress has a profound impact on the brain and is a significant risk factor for many diseases, including cardiovascular and psychiatric disease. Yet, stress is increasing within our daily lives. Understanding precisely how stress leads to disease will be critical to disease prevention.

Impacts of Stress on Mitochondrial Function in the Brain and Body

This research project focuses on how stress affects mitochondria to impact function across different brain regions and ultimately the body, leading to inflammation and hypertension.

We seek to understand how chronic unpredictable stress impacts different areas of the brain in association with different behaviors linked to disease.

We hypothesize that chronic stress will have different effects in females compared to males. Our initial results support this hypothesis as we see unique effects of stress on female mitochondrial function in specific brain regions.


Project Significance

  • It is becoming increasingly evident that mitochondria are more than just the powerhouse of the cell—they are also central to health and disease. Yet how mitochondria might contribute to disease remains unclear.

  • Females have a higher prevalence of stress-related disorders. This research takes both males and females, as well as the female estrous cycle, into account to provide new understanding into the impacts of stress on females—a historically understudied area. This research will lead to new strategies and insights for women's health care.

  • The holistic approach integrates mitochondrial function in the brain with cardiovascular, renal (kidneys), and vascular systems to understand how the brain and body work together in disease.

Research Innovation

We measure mitochondrial function in individual brain regions of both males and females. Females are underrepresented in biomedical research. Our dedication to including sex as a biological variable will yield valuable insights into unique effects of stress on female brain and health.

Research Questions

  1. Does chronic unpredictable stress increase mitochondrial DNA release in the brain and/or periphery?
  2. How do sex hormones interact with stress to affect mitochondrial function?
  3. Will pharmacological blockade of mitochondrial hyperfragmentation prevent the effects of chronic stress on physiology and behavior?
  4. Is chronic stress-evoked mitochondrial dysfunction specific for microglial populations and is there a role for microglial mitochondrial function in stress-induced hypertension?

Purpose: To study how mitochondrial DNA release in the brain links chronic unpredictable stress with sympathetic nervous system hyperactivation

Hypothesis: Chronic unpredictable stress will induce mitochondrial DNA release in specific brain regions within the HPA (hypothalamic-pituitary-adrenal) axis that will trigger an innate immune response activating microglia to promote SNS (sympathetic nervous system) hyperactivity and ultimately hypertension.

Goals: Mitochondrial function is crucial for health. This is especially true in the brain, where neurons are heavily reliant on mitochondria for the energy production to support neuronal function. Each brain region has its own energetic needs. By understanding the impact of stress on mitochondrial function, we can better develop therapies to prevent or counteract the effects of stress.

Vision: New sex-specific strategies, understandings and even therapeutic targets to treat diseases and disorders that are affected by stress


SC Impact

While this research improves the lives of anyone who has cardiovascular disease or knows someone with cardiovascular disease in South Carolina—a high percentage of the population—certain groups will benefit greatly from this focus area and the institute's work at large.

Women and the Female Population

This research will improve the lives of anyone who has cardiovascular disease or knows someone with cardiovascular disease in South Carolina. However, certain groups will greatly benefit from our focus area and the institute's work at large.

Black and African American Communities

High blood pressure disproportionately affects African American communities. This community experiences high heart failure rates despite health providers meeting standard of care guidelines. The institute will shed light on how body responses to everyday situations increase the likelihood of cardiovascular disease in these populations.

Veterans and Those Suffering from PTSD or Trauma

Exposure to trauma affects the body in significant ways, especially the heart and vascular system. Veterans are at higher risk of having a new onset of heart disease compared with non-veterans. This research contributes directly to improving the lives of veterans and those with trauma or PTSD, while adding to the overall knowledge base of care for veterans.


Notable Awards, Outcomes and Practical Uses for this Research 

  • Initial results show sex-specific stress response in at least one area of the brain
  • Biological Psychiatry paper: Gestational stress alters postpartum mitochondrial function in the brain. This research identifies key changes in mitochondrial respiration and inflammation in the postpartum prefrontal cortex following chronic mild unpredictable stress during gestation.
  • American Physiology Summit Presentation: Collaborative, interdisciplinary presentation, April 2023

Institute for Cardiovascular Disease Research

    Challenge the conventional. Create the exceptional. No Limits.