Accumulating evidences have suggested that extracellular vesicles (EVs) are crucial players in the pathogenesis of ischemic brain injury. This study was designed to explore the specific functions of M2 phenotype microglia-derived EVs in ischemic brain injury progression. The expression of microRNA-135a-5p (miR-135a-5p) in M2 microglia-derived EVs was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), followed by the identification of expression relationship among miR-135a-5p, thioredoxin-interacting protein (TXNIP), and nod-like receptor protein 3 (NLRP3) by dual luciferase reporter gene assay. After construction of an oxygen-glucose deprivation/reperfusion (OGD/R) cell model, the effects of miR-135a-5p on the biological characteristics of HT-22 cells were assessed by cell counting kit 8 (CCK-8) assay and flow cytometry. Finally, a mouse model of transient middle cerebral artery occlusion (tMCAO) was established and cerebral infarction volume was determined by triphenyltetrazolium chloride (TTC) staining and the expression of IL-18 and IL-1β in the brain tissue was determined by enzyme-linked immunosorbent assay (ELISA). We found that M2 microglia-derived EVs had high expression of miR-135a-5p, and that miR-135a-5p in M2 microglia-derived EVs negatively regulated the expression of NLRP3 via TXNIP. Overexpression of miR-135a-5p promoted the proliferation but inhibited the apoptosis of neuronal cells, and inhibited the expression of autophagy-related proteins. M2 microglia-derived EVs delivered miR-135a-5p into neuronal cells to inhibit TXNIP expression, which further inhibited the activation of NLRP3 inflammasome, thereby reducing neuronal autophagy and ischemic brain injury. Hence, M2 microglia-derived EVs are novel therapeutic targets for ischemic brain injury treatment.
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http://dx.doi.org/10.1038/s41374-021-00545-1 | DOI Listing |
Int Immunopharmacol
September 2024
Department of Geriatrics, Tianjin Medical University General Hospital, Anshan Road No. 154, Tianjin 300052, China; Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Ministry of Education, Tianjin 300052, China; School of Medicine, Nankai University, Tianjin 300192, China. Electronic address:
Ischemic stroke (IS) is a debilitating neurological disorder with limited treatment options. Extracellular vesicles (EVs) have emerged as crucial lipid bilayer particles derived from various cell types that facilitate intercellular communication and enable the exchange of proteins, lipids, and genetic material. Microglia are resident brain cells that play a crucial role in brain development, maintenance of neuronal networks, and injury repair.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
April 2024
Department of Biology, University of Crete, Heraklion GR71409, Crete, Greece.
Exp Neurol
April 2024
National Research Council of Italy, Institute of Neuroscience (IN-CNR), Via Raoul Follereau 3, 20854 Vedano al Lambro, Italy. Electronic address:
J Neurochem
January 2024
Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Cátedra de Química Biológica Patológica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Microglia (MG) play a crucial role as the predominant myeloid cells in the central nervous system and are commonly activated in multiple sclerosis. They perform essential functions under normal conditions, such as actively surveying the surrounding parenchyma, facilitating synaptic remodeling, engulfing dead cells and debris, and protecting the brain against infectious pathogens and harmful self-proteins. Extracellular vesicles (EVs) are diverse structures enclosed by a lipid bilayer that originate from intracellular endocytic trafficking or the plasma membrane.
View Article and Find Full Text PDFNeurosci Lett
January 2024
Department of Laboratory Medicine, The First Hospital of Lanzhou University, The First School of Clinical Medicine, Lanzhou, 730000, Gansu Province, China. Electronic address:
Parkinson's disease (PD) is characterized by the formation of Lewy body, which mainly contains misfolded α-synuclein. Microglial activation plays a role in neurodegeneration. The pathologically oligomeric α-synuclein promotes inflammatory microglia, while physiologically monomeric α-synuclein induces anti-inflammatory microglia, the relationship between these two forms in activating microglia and the molecular mechanism is essentially unknown.
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