cortisol

Circulating extracellular vesicles as functional indicators of maternal mental and physical health in pregnancy and postpartum

Women with high levels of adverse childhood experiences (ACEs) are at significantly greater risk for negative health outcomes in pregnancy and postpartum, including gestational diabetes, PTB, and depressed mood. However, we still lack biomarkers or a sufficient understanding of causal mechanisms. Extracellular vesicles (EVs) are one of the most dynamic and abundant biological signals secreted into maternal circulation, largely produced by the placenta – where levels increase 4-5-fold during pregnancy. Similarly, removal of the placenta at delivery produces a dramatic drop in maternal EV concentration. Across species, we and others have identified significant EV changes during pregnancy associated with homeostatic regulation, including glucose and glucocorticoid levels, supporting key roles for EVs in maternal health. However, longitudinal studies in human pregnancy and postpartum have not been conducted. We know little as to the mechanisms controlling EV secretion or the roles for EVs in maternal pregnancy and postpartum health. Our decade’s long work identified the X-linked gene, O-glycosyltransferase (OGT), in mouse and human placenta as a master gage of the maternal milieu, where OGT regulation of annexin A1 (AA1) is key to EV cargo loading and secretion from the placenta. We recently reported that placental OGT levels positively correlate with maternal EV concentration. How this association may contribute toward postpartum health, including regulating maternal stress physiology and mood in humans is not known. We hypothesize that increased ACEs, similar to stress in preclinical models, are negatively associated with a cell’s ability to secrete EVs important to maintain homeostasis in the face of the challenges of pregnancy and postpartum, producing an increasingly unhealthy state. Therefore, the goals of these proposed studies in both mice and humans are as follows: 1) To identify cellular mechanisms involved in EV secretion important to maternal health outcomes utilizing the placenta as a tool to genetically target OGT in mice and examine maternal homeostatic control related to EV concentration and composition during pregnancy; 2) To examine the functional ability for a dynamic elevation in maternal EV concentration to improve homeostatic regulation in pregnancy and postpartum using chemogenetic activation (DREADDs) of placenta trophoblast cells in pregnancy, and by EV transfer by tail vein injection postpartum; and 3) To examine in women changes in maternal EVs in a longitudinal pregnancy and postpartum study in association with maternal glucose and cortisol changes, we will examine markers of physical (glucose challenge test), HPA stress (hair cortisol & stress- stimulated salivary cortisol) and psychological (Hamilton Rating Scale for Depression, Perceived Stress Scale) health across pregnancy and the postpartum period in 150 healthy women with varying degrees of exposure to ACEs as measured using the ACE Questionnaire (ACE-Q).

Personalized medicine and predictive health and wellness: Adding the chemical component

Wearable sensors that detect and quantify biomarkers in retrievable biofluids (e.g., interstitial fluid, sweat, tears) provide information on human dynamic physiological and psychological states. This information can transform health and wellness by providing actionable feedback. Due to outdated and insufficiently sensitive technologies, current on-body sensing systems have capabilities limited to pH, and a few high-concentration electrolytes, metabolites, and nutrients. As such, wearable sensing systems cannot detect key low-concentration biomarkers indicative of stress, inflammation, metabolic, and reproductive status.  We are revolutionizing sensing. Our electronic biosensors detect virtually any signaling molecule or metabolite at ultra-low levels. We have monitored serotonin, dopamine, cortisol, phenylalanine, estradiol, progesterone, and glucose in blood, sweat, interstitial fluid, and tears. The sensors are based on modern nanoscale semiconductor transistors that are straightforwardly scalable for manufacturing. We are developing sensors for >40 biomarkers for personalized continuous monitoring (e.g., smartwatch, wearable patch) that will provide feedback for treating chronic health conditions (e.g., perimenopause, stress disorders, phenylketonuria). Moreover, our sensors will enable female fertility monitoring and the adoption of more healthy lifestyles to prevent disease and improve physical and cognitive performance.

Role of Oxytocin in regulating microglia functions to prevent brain damage of the developing brain

Every year, 30 million infants worldwide are delivered after intra-uterine growth restriction (IUGR) and 15 million are born preterm. These two conditions are the leading causes of ante/perinatal stress and brain injury responsible for neurocognitive and behavioral disorders in more than 9 million children each year. Both prematurity and IUGR are associated with perinatal systemic inflammation, a key factor associated with neuroinflammation and identified to be the best predictor of subsequent neurological impairments. Most of pharmacological candidates have failed to demonstrate any beneficial effect to prevent perinatal brain damage. In contrast, environmental enrichment based on developmental care, skin-to-skin contact and vocal/music intervention appears to confer positive effects on brain structure and function. However, mechanisms underlying these effects remain unknown. There is strong evidence that an adverse environment during pregnancy and the perinatal period can influence hormonal responses of the newborn with long-lasting neurobehavioral consequences in infancy and adulthood. Excessive cortisol release in response to perinatal stress induces pro-inflammatory and brain-programming effects. These deleterious effects are known to be balanced by Oxytocin (OT), a neuropeptide playing a key role during the perinatal period and parturition, in social behavior and regulating the central inflammatory response to injury in the adult brain. Using a rodent model of IUGR associated with perinatal brain damage, we recently reported that Carbetocin, a brain permeable long-lasting OT receptor (OTR) agonist, was associated with a significant reduction of activated microglia, the primary immune cells of the brain. Moreover this reduced microglia reactivity was associated to a long-term neuroprotection. These findings make OT a promising candidate for neonatal neuroprotection through neuroinflammation regulation. However, the causality between the endogenous OT and central inflammation response to injury has not been established and will be further studied by the lab.

Altered Cortisol Awakening Response in Relationship with Trauma in Functional Neurological Disorders

Cortisol in Cortisol Levels Across the Lifespan in Common Marmosets (Callithrix jacchus)

Burnout syndrome in the staff of different institutions correlated with EEG-EKG and cortisol post-COVID 19 pandemic

FENS Forum 2024

Exploring the influence of maternal prenatal depressive symptoms and hair cortisol concentration on infant corpus callosum integrity

FENS Forum 2024

Impact of chronic stress and cortisol on hippocampal neuroplasticity: Implications for depression

FENS Forum 2024

Plasma cortisol levels of male and female rats with different levels of experience with ethanol

FENS Forum 2024

Role of testosterone and cortisol in formula car drivers for achieving high performance in a real competitive situation

FENS Forum 2024