Spaceflight suppresses inflammasome signaling and alters dopaminergic regulation in the mouse brain from Rodent Research-1 (RR-1) mission.
10 affiliations
- 1Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, Brownsville, TX, USA.
- 2Department of Neurosurgery, Center of Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA.
- 3Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA.
- 4Department of Psychological Science, University of Texas Rio Grande Valley, Brownsville, TX, USA.
- 5Department of Neuroscience and Institute of Neuroscience, University of Texas Rio Grande Valley School of Medicine, Harlingen, TX, USA.
- 6Department of Basic Sciences, Division of Biomedical Engineering Sciences (BMES), Loma Linda University, Loma Linda, CA, USA.
- 7Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA.
- 8Department of Cellular Physiology and Molecular Biophysics, University of Miami Miller School of Medicine, Miami, FL, USA.
- 9Department of Medicine - Clinical Pharmacology, Vanderbilt Brain Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
- 10Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, Brownsville, TX, USA. [email protected].
Abstract
Microgravity and radiation exposure during spaceflight pose significant health risks to astronauts, including disruption of physiological and neural homeostasis and increased risk of neurodegenerative disorders. Spaceflight induces neuroinflammatory responses, including inflammasome formation, which regulates innate immune signaling following cellular damage. Additionally, reduced neuromuscular activity in microgravity is associated with altered dopamine signaling. However, the direct effect on inflammasome activation and dopaminergic regulation under spaceflight is still poorly understood. In this study, we examined the genes and proteins that are associated with the inflammasome and the dopamine dysregulation associated with inflammation in mice exposed to spaceflight conditions. Mouse brains (C57BL/6J) from Rodent Research 1 (RR1, SpaceX-4) missions were analyzed based on exposure to spaceflight, simulated, and standard conditions for a baseline and control. Brain samples were analyzed for gene expression of inflammasome signaling genes and for mRNA expression to detect alterations under spaceflight conditions. Dopamine analysis was also performed to identify possible changes in major monoamines. This observation indicated that spaceflight conditions were associated with suppressed inflammasome-related gene expression with no statistically observable changes in monoamine concentration. Overall, the data established that spaceflight stressors concurrently dampen neuroinflammatory signaling while altering dopamine regulation in the brain.
Graphical abstract: Inflammasome activation under internal and external signaling. (1) The spaceflight environment (Space radiation/microgravity) causes oxidative stress, and through that, (2) it activates NF-κB, which transcribes NLRP3, Pro-Caspase-1, and Pro-IL-1β. NLRP3 and Pro-Caspase-1, with the help of ASC, (3) form the Inflammasome complex, which cleaves Pro-Caspase-1 to form active Caspase-1. (4) The Active Caspase-1 activates both Pro-IL-1β and GSDMD to N-GSDMND. The N-GSDMND form a complex on the neuron cell surface and create pores, (5), allowing IL-1β and other cytokines to be released and induce pyroptosis. (6) The released cytokines act as signaling for the surface cell receptors and activate the DAMP pathways, and the cycle continues. (5 A) IL-1β also inhibits monoaminergic synthesis and decreases the amount of DA, 5-HT, and NE in the cell (6 A) and reduces the anti-inflammatory effects. DJ1 in the cell acts as a neuroprotector against oxidative stress, so it inhibits the activation of the inflammasome transcription through ROS activation. It also helps the inhibition of monoaminergic synthesis, which allows the neurotransmitters to continue their anti-inflammatory effects.
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BibTeX
@article{rodriguez2026spaceflight,
title = {{Spaceflight suppresses inflammasome signaling and alters dopaminergic regulation in the mouse brain from Rodent Research-1 (RR-1) mission.}},
author = {Angel A Rodriguez and Deepa Roy and Marissa Burke and Mario Gil and Xiao Wen Mao and Juan Pablo de Rivero Vaccari and Christopher E Mason and Ginger Milne and Upal Roy},
journal = {Journal of neuroinflammation},
year = {2026},
month = aug,
doi = {10.1186/s12974-026-03913-0},
url = {https://europepmc.org/article/MED/42963800},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Spaceflight suppresses inflammasome signaling and alters dopaminergic regulation in the mouse brain from Rodent Research-1 (RR-1) mission.
AU - Angel A Rodriguez
AU - Deepa Roy
AU - Marissa Burke
AU - Mario Gil
AU - Xiao Wen Mao
AU - Juan Pablo de Rivero Vaccari
AU - Christopher E Mason
AU - Ginger Milne
AU - Upal Roy
PY - 2026
DA - 2026/08/04
JO - Journal of neuroinflammation
DO - 10.1186/s12974-026-03913-0
UR - https://europepmc.org/article/MED/42963800
AB - Microgravity and radiation exposure during spaceflight pose significant health risks to astronauts, including disruption of physiological and neural homeostasis and increased risk of neurodegenerative disorders. Spaceflight induces neuroinflammatory responses, including inflammasome formation, which regulates innate immune signaling following cellular damage. Additionally, reduced neuromuscular activity in microgravity is associated with altered dopamine signaling. However, the direct effect on inflammasome activation and dopaminergic regulation under spaceflight is still poorly understood. In this study, we examined the genes and proteins that are associated with the inflammasome and the dopamine dysregulation associated with inflammation in mice exposed to spaceflight conditions. Mouse brains (C57BL/6J) from Rodent Research 1 (RR1, SpaceX-4) missions were analyzed based on exposure to spaceflight, simulated, and standard conditions for a baseline and control. Brain samples were analyzed for gene expression of inflammasome signaling genes and for mRNA expression to detect alterations under spaceflight conditions. Dopamine analysis was also performed to identify possible changes in major monoamines. This observation indicated that spaceflight conditions were associated with suppressed inflammasome-related gene expression with no statistically observable changes in monoamine concentration. Overall, the data established that spaceflight stressors concurrently dampen neuroinflammatory signaling while altering dopamine regulation in the brain. Graphical abstract: Inflammasome activation under internal and external signaling. (1) The spaceflight environment (Space radiation/microgravity) causes oxidative stress, and through that, (2) it activates NF-κB, which transcribes NLRP3, Pro-Caspase-1, and Pro-IL-1β. NLRP3 and Pro-Caspase-1, with the help of ASC, (3) form the Inflammasome complex, which cleaves Pro-Caspase-1 to form active Caspase-1. (4) The Active Caspase-1 activates both Pro-IL-1β and GSDMD to N-GSDMND. The N-GSDMND form a complex on the neuron cell surface and create pores, (5), allowing IL-1β and other cytokines to be released and induce pyroptosis. (6) The released cytokines act as signaling for the surface cell receptors and activate the DAMP pathways, and the cycle continues. (5 A) IL-1β also inhibits monoaminergic synthesis and decreases the amount of DA, 5-HT, and NE in the cell (6 A) and reduces the anti-inflammatory effects. DJ1 in the cell acts as a neuroprotector against oxidative stress, so it inhibits the activation of the inflammasome transcription through ROS activation. It also helps the inhibition of monoaminergic synthesis, which allows the neurotransmitters to continue their anti-inflammatory effects.
SN - 1742-2094
ER -