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Updated: Jan 4, 2026
Author Spotlight: In Vitro Co-Culture Model for Studying Microglia-Neuronal Interactions in Disease Conditions
Published on: July 26, 2024
Neuron-derived exosomes with high miR-21-5p expression promoted polarization of M1 microglia in culture
Zhenyu Yin1, Zhaoli Han1, Tianpeng Hu1
1Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Institute of Geriatrics, Tianjin, China.
Background:
Neuroinflammation is a characteristic pathological change of acute neurological deficit and chronic traumatic encephalopathy (CTE) after traumatic brain injury (TBI). Microglia are the key cell involved in neuroinflammation and neuronal injury. The type of microglia polarization determines the direction of neuroinflammation. MiR-21-5p elevated in neurons and microglia after TBI in our previous research. In this study, we explore the influence of miR-21-5p for neuroinflammation by regulating microglia polarization.
Methods:
In this study, PC12 and BV2 used to instead of neuron and microglia respectively. The co-cultured transwell system used to simulate interaction of PC12 and BV2 cells in vivo environment.
Results:
We found that PC12-derived exosomes with containing miR-21-5p were phagocytosed by microglia and induced microglia polarization, meanwhile, the expression of miR-21-5p was increased in M1 microglia cells. Polarization of M1 microglia aggravated the release of neuroinflammation factors, inhibited the neurite outgrowth, increased accumulation of P-tau and promoted the apoptosis of PC12 cells, which formed a model of cyclic cumulative damage. Simultaneously, we also got similar results in vivo experiments.
Conclusions:
PC12-derived exosomes with containing miR-21-5p is the essential of this cyclic cumulative damage model. Therefore, regulating the expression of miR-21-5p or the secretion of exosomes may be an important novel strategy for the treatment of neuroinflammation after TBI.
Insights
MicroRNA-21-5p in exosomes from injured neurons drives neuroinflammation by polarizing microglia. Targeting this pathway may treat traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Neuroinflammation is a key factor in traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).
- Microglia polarization dictates the neuroinflammatory response.
- MiR-21-5p is upregulated in neurons and microglia post-TBI.
Purpose of the Study:
- To investigate the role of miR-21-5p in regulating microglia polarization and neuroinflammation after TBI.
- To explore the therapeutic potential of targeting miR-21-5p or exosome secretion.
Main Methods:
- Utilized PC12 (neuronal) and BV2 (microglial) cell lines in a co-cultured transwell system.
- Investigated the effects of PC12-derived exosomes containing miR-21-5p on microglia polarization.
- Validated findings through in vivo experiments.
Main Results:
- PC12-derived exosomes containing miR-21-5p induced M1 microglia polarization.
- M1 microglia exacerbated neuroinflammation, inhibited neurite outgrowth, increased P-tau accumulation, and promoted apoptosis.
- These effects formed a cyclic cumulative damage model, confirmed in vivo.
Conclusions:
- PC12-derived exosomal miR-21-5p is crucial for the observed cyclic damage model post-TBI.
- Modulating miR-21-5p expression or exosome secretion offers a novel therapeutic strategy for TBI-induced neuroinflammation.
