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Updated: Jul 5, 2026
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Simulated microgravity affects neuronal synaptic plasticity by regulating microglial pro-inflammatory activation
Xuechai Chen1, Chunsen Yuan2, Zihan Li2
1Beijing International Science and Technology Cooperation Base for Antiviral Drugs, College of Chemistry and Life Science, Beijing University of Technology, Beijing, China. chenxuechai@bjut.edu.cn.
Abstract:
As resident immune cells of the central nervous system, microglia exhibit inherent responsiveness to external stimuli and insults. In this study, we demonstrated that a simulated microgravity conditions induces pro-inflammatory activation of BV2 microglial cells, a process tightly regulated by the RhoA GTPase Arhgap18. Specifically, the downregulation of Arhgap18 under simulated microgravity was identified as the upstream mechanism driving microglial activation and triggering neuroinflammation via the Arhgap18/RhoA/ROCK signaling pathway. For in vivo validation, we established a 21-day hindlimb unloading (HU) mouse model, which confirmed that simulated microgravity promotes pro-inflammatory microglial activation in the cerebral cortex and hippocampus. Furthermore, co-culture of N2a neural cells with pro-inflammatory microglia led to distinct morphological alterations in N2a cells and a significant downregulation of synaptic plasticity-related proteins-effects that were recapitulated in the HU mouse model. Collectively, these findings suggest that microgravity may mediate changes in neuronal synaptic plasticity by activating the inflammatory response of microglia.
Insights
Simulated microgravity activates microglia, initiating neuroinflammation via Arhgap18 downregulation. This microglial activation impacts neuronal synaptic plasticity, suggesting a link between spaceflight conditions and brain health.
Area of Science:
- Neuroscience
- Immunology
- Space Biology
Background:
- Microglia are the primary immune cells in the central nervous system.
- Microglia are sensitive to environmental changes and insults.
- Understanding microglial responses to microgravity is crucial for astronaut health.
Purpose of the Study:
- To investigate the effect of simulated microgravity on microglial activation.
- To identify the molecular mechanisms underlying microglial activation under microgravity.
- To assess the impact of microgravity-induced microglial activation on neuronal function.
Main Methods:
- Utilized BV2 microglial cell cultures under simulated microgravity.
- Investigated the role of RhoA GTPase Arhgap18 in microglial activation.
- Employed a 21-day hindlimb unloading (HU) mouse model for in vivo studies.
- Performed co-culture experiments with N2a neural cells and activated microglia.
Main Results:
- Simulated microgravity induced pro-inflammatory activation of BV2 microglial cells.
- Downregulation of Arhgap18 was identified as the upstream mechanism driving microglial activation via the Arhgap18/RhoA/ROCK pathway.
- In vivo hindlimb unloading confirmed pro-inflammatory microglial activation in the mouse brain.
- Pro-inflammatory microglia impaired N2a cell morphology and reduced synaptic plasticity proteins.
Conclusions:
- Microgravity promotes pro-inflammatory microglial activation, mediated by Arhgap18 downregulation.
- Activated microglia under microgravity conditions negatively affect neuronal synaptic plasticity.
- These findings highlight a potential mechanism linking microgravity-induced neuroinflammation to changes in brain function.
