Neuron-derived exosomes with high miR-21-5p expression promoted polarization of M1 microglia in culture

Abstract

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.

Keywords: Exosome; Microglia polarization; Neuroinflammation; TBI; miR-21-5p.