Galactic cosmic ray particle exposure does not increase inflammation or oxidative stress in rat microglial cells in vitro

Authors: CAHOON, DANIELLE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Fisher, Derek; RABIN, BERNARD - University Of Maryland; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ZHENG, TONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Shukitt-Hale, Barbara

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/27/2024
Publication Date: 5/29/2024
Citation: Cahoon, D., Fisher, D.R., Rabin, B.M., Lamon-Fava, S., Wu, D., Zheng, T., Shukitt Hale, B. 2024. Galactic cosmic ray particle exposure does not increase inflammation or oxidative stress in rat microglial cells in vitro. International Journal of Molecular Sciences. 25(11):5923. https://doi.org/10.3390/ijms25115923.
DOI: https://doi.org/10.3390/ijms25115923

Interpretive Summary: Astronauts in deep space will be exposed to radiation particles which have been shown to negatively affect the brain by increasing inflammation and oxidative stress. There are cells in the brain called microglia which regulate inflammation. This study used a model of microglia which were radiated with helium or iron particles with the goal of establishing a model for testing possible countermeasures. However, results showed that radiation with either particle did not increase measures of oxidative stress and inflammation compared to non-irradiated cells. Findings suggest that microglia in isolation may not be the primary cause of neuroinflammation and OS following radiation exposures.

Technical Abstract: Astronauts on exploratory missions will be exposed to galactic cosmic rays (GCR), which include helium (4He) and 56Fe particles. Exposure to GCR can induce neuroinflammation and oxidative stress (OS) and may increase risk for neurodegenerative disease. As key regulators of inflammation and OS in the central nervous system (CNS), microglial cells may be involved in GCR-induced deficits, and therefore could be a target for neuroprotection. This study assessed the effects of exposure to 4He and 56Fe particles on inflammation and OS in microglia in vitro, with the goal of establishing a model for testing countermeasure efficacy. Rat microglia were exposed to a single dose of 20 cGy (300 MeV/n) 4He or 2 Gy 56Fe (600 MeV/n), while control cells were not exposed to radiation (0 cGy). Immediately following irradiation, fresh media was applied to the cells, and outcomes were assessed 24 hours later. Biomarkers of inflammation (cyclooxygenase-2 [COX-2], nitric oxide synthase [iNOS], phosphorylated I'B-a [pI'B-'], tumor necrosis factor-' [TNF'], and nitrite [NO2-]) and OS (NADPH oxidase [NOX2]) were assessed using standard immunochemical techniques. Results showed that radiation did not increase protein expression of COX-2, iNOS, pI'B-', TNF', NO2- or NOX2 compared to non-irradiated control conditions in microglial cells (P > 0.05). Findings suggest that microglia in isolation may not be the primary cause of neuroinflammation and OS following GCR exposures. Future work identifying alternative cellular targets and mechanisms is necessary to advance the development of countermeasures against the neurodegenerative effects of GCR particle exposure.