ArticleInternational journal of molecular sciences2021
Rac1/Wave2/Arp3 Pathway Mediates Rat Blood-Brain Barrier Dysfunction under Simulated Microgravity Based on Proteomics Strategy.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Pathogens of the Human Central Nervous System-the Major Protozoan Parasites and Helminths.Molecular neurobiology · 2026Review
- NCKAP1 coordinates focal adhesion and adherens junction dynamics in endothelial barrier maintenance and angiogenesis.iScience · 2026Article
- Pathogens of the human central nervous system-the major viral pathogens.Journal of neurovirology · 2026Review
- Pathogens of the Human Central Nervous System- the Major Bacterial Pathogens.Molecular neurobiology · 2026Review
- Microgravity and cancer cells: from molecular mechanisms to therapeutic strategies.Cell death discovery · 2026Review
- A systematic review of the cerebrovascular adaptations following exposure to spaceflight or ground-based analogs: lessons from human and animal studies.NPJ microgravity · 2025Article
- Review of microgravity's impact on cardiovascular and nervous systems in space exploration.NPJ microgravity · 2025Review
- Cerebral proteome adaptations to amyloid angiopathy are prevented by carbonic anhydrase inhibitors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Oxidative Stress on the Ground and in the Microgravity Environment: Pathophysiological Effects and Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.Military Medical Research · 2024Review
- Simulated microgravity-induced dysregulation of cerebrospinal fluid immune homeostasis by disrupting the blood-cerebrospinal fluid barrier.Brain and behavior · 2024Article
- Physical exercise restores adult neurogenesis deficits induced by simulated microgravity.NPJ microgravity · 2024Article
- Organs in orbit: how tissue chip technology benefits from microgravity, a perspective.Frontiers in lab on a chip technologies · 2024Article
- Microglial activation in spaceflight and microgravity: potential risk of cognitive dysfunction and poor neural health.Frontiers in cellular neuroscience · 2024Review
- Reduced Brain Cortex Angiogenesis in the Offspring of the Preeclampsia-Like Syndrome.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Simulated Microgravity Alters P-Glycoprotein Efflux Function and Expression via the Wnt/β-Catenin Signaling Pathway in Rat Intestine and Brain.International journal of molecular sciences · 2023Article
- Article
- Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway.NPJ science of food · 2022Article
- PINK1-Dependent Mitophagy Reduced Endothelial Hyperpermeability and Cell Migration Capacity Under Simulated Microgravity.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Rats were tail-suspended to simulate MG for 21 days. SMG could disrupt the BBB, including increased oxidative stress levels, proinflammatory cytokine levels, and permeability, damaged BBB ultrastructure, and downregulated tight junctions (TJs) and adherens junctions (AJs) protein expression in the rat brain. A total of 554 differentially expressed proteins (DEPs) induced by SMG were determined based on the label-free quantitative proteomic strategy. The bioinformatics analysis suggested that DEPs were mainly enriched in regulating the cell-cell junction and cell-extracellular matrix biological pathways. The inhibited Ras-related C3 botulinum toxin substrate 1 (Rac1)/Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 (Wave2)/actin-related protein 3 (Arp3) pathway and the decreased ratio of filamentous actin (F-actin) to globular actin contributed to BBB dysfunction induced by SMG. In the human brain microvascular endothelial cell (HBMECs), SMG increased the oxidative stress levels and proinflammatory cytokine levels, promoted apoptosis, and arrested the cell cycle phase. Expression of TJs and AJs proteins were downregulated and the distribution of F-actin was altered in SMG-treated HBMECs. The key role of the Rac1/Wave2/Arp3 pathway in BBB dysfunction was confirmed in HBMECs with a specific Rac1 agonist. This study demonstrated that SMG induced BBB dysfunction and revealed that Rac1/Wave2/Arp3 could be a potential signaling pathway responsible for BBB disruption under SMG. These results might shed a novel light on maintaining astronaut CNS homeostasis during space travel.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.