Administering extracellular vesicles derived from human stem cells through the nose to aged mice reduces inflammation in the hippocampus and improves cognitive performance by inhibiting specific...
Mechanism
Synthesis from 1 study
Stem cell packages sprayed into the nose reach the brain’s immune cells and turn off two harmful inflammation switches. When these switches are off, the immune cells stop damaging brain connections, allowing memory and thinking to improve.
Most probable mechanism
Tiny packages from stem cells, sprayed into the nose, travel to the brain and enter immune cells there. These packages carry special molecules that block two harmful signaling systems inside the cells, which normally cause inflammation and damage. When these systems are turned off, the immune cells calm down, produce fewer toxic chemicals, and stop harming brain connections. As a result, the brain can remember things better.
hiPSC-NSC-EVs are taken up by microglia in the hippocampus after intranasal delivery
miR-30e-3p from EVs binds to NLRP3 mRNA, suppressing translation and reducing NLRP3 protein levels
Reduced NLRP3 protein impairs assembly of the NLRP3-ASC-caspase-1 inflammasome complex
Inflammasome assembly failure prevents caspase-1 activation and maturation of IL-1β and IL-18
miR-181a-5p from EVs binds to STING mRNA, suppressing translation and reducing STING protein levels
Reduced STING protein impairs oligomerization and prevents TBK1 and IRF3 phosphorylation
Inactive IRF3 fails to drive transcription of type I interferons (e.g., IFN-α)
Reduced IFN-α leads to diminished phosphorylation of JAK1, JAK2, and STAT1, suppressing interferon-stimulated gene expression
Suppression of NLRP3 and cGAS-STING pathways reduces microglial oxidative stress and proinflammatory cytokine release
Reduced inflammation and oxidative stress restore mitochondrial gene expression and ATP production in microglia
Improved microglial homeostasis preserves synaptic integrity and neuronal function in the hippocampus and perirhinal cortex
Preserved neuronal function enables normal recognition and spatial memory formation
Evidence from Studies
Supporting (1)
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Intranasal Human NSC‐Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS‐STING Signalling, in Aged Hippocampus
Contradicting (0)
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