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Setting-up an In Vitro Model of Rat Blood-brain Barrier BBB: A Focus on BBB Impermeability and Receptor-mediated Transport
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Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics
Ranran Yan1, Huayan Liu1, Fang Lv1
1School of Life Science, Beijing Institute of Technology, No. 5 Zhongguancun South Street, Haidian District, Beijing 100081, China.
International Journal of Molecular Sciences
|June 2, 2021
Summary
Simulated microgravity disrupts the blood-brain barrier (BBB) by increasing oxidative stress and decreasing tight junction proteins. The Rac1/Wave2/Arp3 pathway is identified as a key mechanism contributing to this BBB dysfunction.
Area of Science:
- Neuroscience
- Space Biology
- Proteomics
Background:
- The blood-brain barrier (BBB) is crucial for central nervous system (CNS) homeostasis.
- The impact of microgravity (MG) on BBB integrity is not well understood.
Purpose of the Study:
- To investigate the effects of simulated microgravity (SMG) on the BBB.
- To explore the underlying molecular mechanisms using a proteomic approach.
Main Methods:
- Rats were subjected to tail suspension for 21 days to simulate MG.
- Proteomic analysis identified differentially expressed proteins (DEPs).
- Human brain microvascular endothelial cells (HBMECs) were used to validate findings.
Main Results:
- SMG disrupted the BBB, increasing oxidative stress, inflammation, and permeability.
- SMG downregulated tight junction (TJ) and adherens junction (AJ) proteins.
- The Rac1/Wave2/Arp3 pathway was identified as a key mediator of SMG-induced BBB dysfunction.
Conclusions:
- SMG causes significant BBB dysfunction.
- The Rac1/Wave2/Arp3 pathway plays a critical role in SMG-induced BBB disruption.
- Findings may inform strategies to maintain astronaut CNS health during space travel.
