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12 March 2019 : Laboratory Research  

Exosomes from MiR-21-5p-Increased Neurons Play a Role in Neuroprotection by Suppressing Rab11a-Mediated Neuronal Autophagy In Vitro After Traumatic Brain Injury

Dai Li12BEG, Shan Huang12BC, Jialin Zhu3BEF, Tianpeng Hu12B, Zhaoli Han12B, Shishuang Zhang12C, Jing Zhao12C, Fanglian Chen45AG, Ping Lei12A*

DOI: 10.12659/MSM.915727

Med Sci Monit 2019; 25:1871-1885

Abstract

BACKGROUND: Traumatic brain injury (TBI) produces a series of pathological processes. Recent studies have indicated that autophagy pathway is persistently activated after TBI, which may lead to deterioration of nerve injury. Our preliminary work found miR-21-5p was upregulated in both in vivo and in vitro TBI models. MicroRNAs (miRNAs) could be loaded into exosomes to perform cell-to-cell interactions. This research aimed to evaluate the therapeutic effect of neuron-derived exosomes enriched with miR-21-5p on the TBI in vitro and to further explore the possible mechanisms.

MATERIAL AND METHODS: Brain extracts harvested from an rTBI mouse model were added to cultured HT-22 neurons to imitate the microenvironment of injured brain on in vitro cultured cells. Ultracentrifugation was performed to isolate exosomes. Transmission electron microscopy and Nano sight technology were used to examine exosomes. An in vitro model of TBI was established to study the effect of exosomal miR-21-5p on nerve injury and on neuronal autophagy regulation.

RESULTS: The expression of miR-21-5p was increased in exosomes derived from HT-22 neurons after treatment with rTBI mouse brain extracts. Autophagy was activated in HT-22 neurons after scratch injury. Exosomal miR-21-5p produced a protective effect by suppressing autophagy in a TBI model in vitro. MiR-21-5p could directly target the Rab11a 3’UTR region to reduce its translation and further suppressed Rab11a-mediated neuronal autophagy.

CONCLUSIONS: The levels of miR-21-5p in neuronal exosomes increased from the acute to the chronic phase of TBI. Neuronal exosomes enriched with miR-21-5p can inhibit the activity of neuronal autophagy by targeting Rab11a, thus attenuating trauma-induced, autophagy-mediated nerve injury in vitro.

Keywords: Autophagy, Brain Injuries, exosomes, MicroRNAs, Brain, Brain Injuries, Traumatic, Cells, Cultured, Mice, Inbred C57BL, Neurons, neuroprotection, rab GTP-Binding Proteins

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750