Investigating the Relationship between Immune Function and Adrenal Hormones following Simulated Ionizing Radiation

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Abstract

Upcoming exploration missions will expose humans to extreme environmental conditions with known biological consequences. The unique environment of space includes low-dose, ionizing radiation, microgravity, and social isolation, which can impact metabolic processes that are regulated by adrenal hormones and immunity. Responses to the unique stressors of space also depend on diurnal fluctuations and kinetics that are difficult to interpret without longitudinal monitoring of such changes. Therefore, this research assessed the immune and endocrine system responses of male and female mice exposed to acute, 5-ion galactic cosmic ray radiation (15 cGy), 14-days of hindlimb unloading (HU), and social isolation at multiple time points post-exposure. With an overall goal to identify key biomarkers of interest for future spaceflight mitigation strategies, sex-specific and diurnal responses were characterized to drive down on complex interactions and kinetics between different experimental cohorts. We hypothesize that male mice may experience exacerbated responses, due to recognized elevated inflammatory responses and disproportionate hormonal regulation patterns, compared to their female counterparts. We also hypothesize that combined spaceflight stressors would display elevated responses compared to single exposures. To test this, whole blood analysis of lymphocytes (Tcytotoxic and Thelper cells), monocytes, and neutrophils differentials were performed, along with functional measurements at 24-hours post-irradiation and on day 14 of HU. Adrenal hormones, including corticosterone, aldosterone, DHEA-S, epinephrine, and norepinephrine, were correlated to immune differential counts, while assessment of diurnal patterns of expression were also determined. Future studies aim to perform an immunohistochemical assessment of adrenals and whole transcriptome shotgun RNA sequencing of adrenals and blood to complement these results and pinpoint altered adrenal protein and gene expression patterns involved in hormonal biosynthesis. Collectively, these studies identified sex-specific responses to simulated spaceflight exposures that shape immune function with distinct adrenal hormone regulation. Advancements with this research can direct personalized medicine and pharmaceutical approaches for future exploration missions.

 

Investigating the Relationship between Immune Function and Adrenal Hormones following Simulated Ionizing Radiation

Upcoming exploration missions will expose humans to extreme environmental conditions with known biological consequences. The unique environment of space includes low-dose, ionizing radiation, microgravity, and social isolation, which can impact metabolic processes that are regulated by adrenal hormones and immunity. Responses to the unique stressors of space also depend on diurnal fluctuations and kinetics that are difficult to interpret without longitudinal monitoring of such changes. Therefore, this research assessed the immune and endocrine system responses of male and female mice exposed to acute, 5-ion galactic cosmic ray radiation (15 cGy), 14-days of hindlimb unloading (HU), and social isolation at multiple time points post-exposure. With an overall goal to identify key biomarkers of interest for future spaceflight mitigation strategies, sex-specific and diurnal responses were characterized to drive down on complex interactions and kinetics between different experimental cohorts. We hypothesize that male mice may experience exacerbated responses, due to recognized elevated inflammatory responses and disproportionate hormonal regulation patterns, compared to their female counterparts. We also hypothesize that combined spaceflight stressors would display elevated responses compared to single exposures. To test this, whole blood analysis of lymphocytes (Tcytotoxic and Thelper cells), monocytes, and neutrophils differentials were performed, along with functional measurements at 24-hours post-irradiation and on day 14 of HU. Adrenal hormones, including corticosterone, aldosterone, DHEA-S, epinephrine, and norepinephrine, were correlated to immune differential counts, while assessment of diurnal patterns of expression were also determined. Future studies aim to perform an immunohistochemical assessment of adrenals and whole transcriptome shotgun RNA sequencing of adrenals and blood to complement these results and pinpoint altered adrenal protein and gene expression patterns involved in hormonal biosynthesis. Collectively, these studies identified sex-specific responses to simulated spaceflight exposures that shape immune function with distinct adrenal hormone regulation. Advancements with this research can direct personalized medicine and pharmaceutical approaches for future exploration missions.