Our overall objective is to determine the short- and long-term risks of radiation from the space environment on cognition, motor abilities, fatigue resistance, anxiety, and changes in the brain and…

This is a $2,476,960 grant award from the National Aeronautics and Space Administration (NASA) to Brigham & Women's Hospital Inc., a research hospital affiliated with Harvard Medical School. The grant will fund a 4-year research study to determine the short- and long-term effects of various types of space radiation, including iron, proton, oxygen-16, and mixed beams, on cognition, motor abilities, fatigue, anxiety, and cardiovascular and brain health in Alzheimer's disease mouse models. The research will be conducted in collaboration with investigators at Washington University, Duke University, and New York University. The study will also evaluate the use of 3D neural organoid models to assess acute and long-term central nervous system effects of space radiation. This grant award is not associated with a set-aside contract vehicle. The prime contractor, Brigham & Women's Hospital Inc., is a subsidiary of the larger Partners Healthcare System Incorporated (also known as Mass General Brigham), a prominent healthcare and research organization in Boston.

Our overall objective is to determine the short- and long-term risks of radiation from the space environment on cognition, motor abilities, fatigue resistance, anxiety, and changes in the brain and cardiovascular system. Over the past 3 years, we have determined that low-dose 56FE (iron) radiation has long-term, SEX-specific consequences on cognition, locomotion, neuroinflammation and alzheimer􀁊s disease (ad) pathogenesis, with males being more vulnerable than females. Analysis of proton-irradiated mice is underway. Over the past year, we have developed a collaboration with DR. Doris taylor (texas heart institute), CO-i on this proposal, by sharing the heart, one kidney and bone marrow from each of the mice irradiated in three of our studies. Over the next 4 years, we will extend our research by comparing our existing data from our current studies on the late central nervous system (CNS) and cardiovascular (CV) effects of a single dose of iron radiation or a single dose of protons with a single dose of oxygen-16 or mixed beam GCR (protons, oxygen-16 and iron) in male and female ad-like transgenic and wildtype mice, and gamma irradiated wildtype mice (aim 1). In addition, we will examine the SEX- and APO e-specific late CNS and CV dose-specific effects of iron radiation in the same ad-like mouse model modified by targeted replacement of murine APO e with human APO E3 or E4 to determine if human APOE4, a strong risk factor for ad and CV disease, exacerbates the effects of radiation (aim 2). This work will be conducted in collaboration with investigators at wash u, duke u and NYU. We will perform longitudinal magnetic resonance imaging (MRI) on the brain and heart in a subset of mice in aims 1 and 2 to determine radiation-induced changes within individual animals. In addition, mice will undergo extensive behavioral testing as well as pathological and biochemical analysis of brain and heart. Lastly, we will conduct a study to test 2 novel human 3D neural organoid models of alzheimer􀁊s disease, developed by our collaborators at MGH and MIT (aim 3), for acute and late CNS effects of space radiation on neuronal health, amyloid plaques, TAU pathology and epigenetics, and to investigate the potential of these models for screening mitigating treatments in the future. In collaboration with DR. Taylor, we will also irradiate undifferentiated induced pluripotent stem cells (ipscs) from human males and females to determine whether highly charged, high energy (HZE) particle irradiation alters their ability to differentiate into cardiomyocytes, morphology and/or maturation. In summary, we propose to take our current studies to the next logical step in an effort to better understand the potential risks of galactic cosmic radiation (GCR) to the brain and cardiovascular system in order to prepare astronauts for long-term deep space mission, including missions to mars.