Update on the roles and applications of extracellular vesicles in depression

Figure 3 A summary of validated roles of extracellular vesicles derived from different sources in depression. (1) Astrocyte-derived extracellular vesicles (EVs) containing Apo-D act on neurons in the brain and play a neuroprotection role under oxidative stress; (2) Neuron-derived EVs containing miRNAs act on microglia; (3) Neuron-derived EVs containing miR-135a-3p, miR-6790-3p, and miR-11399 act on astrocytes to promote neuronal regeneration; (4) Neuron-derived EVs containing miR-9-5p promote M1 microglial polarization and neuronal damage; (5) Neurons stimulated by BDNF-derived EVs containing miR-132-5p, miR-218-5p, and miR-690 act on neurons and increase excitatory synapse clustering; (6) Microglia-derived EVs containing miR-146a-5p act on neurons and inhibit neurogenesis; (7) Oligodendrocyte-derived EVs containing sirtuin 2 act on neurons, promoting neurogenesis and synaptic plasticity; (8) Bone marrow mesenchymal stem cell-derived EVs containing miR-26a act on neurons and promote neuronal proliferation; (9) NK EVs containing miR-207 act on astrocytes and reduce neuroinflammation; (10) Neural stem cell-derived EVs containing miR-16-5p inhibit neuron apoptosis; (11) Aggregatibacter actinomycetemcomitans-derived EVs containing exRNA act on microglia and promote neuroinflammation; (12) Serum-derived EVs act on neurons, promoting neuronal proliferation and neurogenesis; (13) Astrocyte-derived EVs in plasma act on neurons and promote neuroinflammation; (14) EVs derived from blood act on neuronal stem cells and promote neuronal differentiation; and (15) Brain-derived EVs transfer to the periphery through the blood-brain barrier, with abnormal expression of certain proteins and miRNAs observed in blood. BDNF: Brain-derived neurotrophic factor; IL: Interleukin; TNF-α: Tumor necrosis factor α; BMSCs: Bone marrow mesenchymal stem cells; NSCs: Neural stem cells; SIRT2: Sirtuin 2; Aa: Aggregatibacter actinomycetemcomitans. Created by Biorender.