Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury
Mild hypothermia has been proven to inhibit microglia activation after TBI. Exosomal microRNA derived from microglia played a critical role in promoting neurite outgrowth and synapse recovery. Here, we aimed to investigate the role of microRNAs in microglial exosomes after hypothermia treatment on n...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123000566 |
| _version_ | 1797867418240942080 |
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| author | Chuanfang Wang Yunxiang Ji Huabin Zhang Yongyi Ye Guilong Zhang Shizhen Zhang Chengcheng Zhao Yezhong Wang |
| author_facet | Chuanfang Wang Yunxiang Ji Huabin Zhang Yongyi Ye Guilong Zhang Shizhen Zhang Chengcheng Zhao Yezhong Wang |
| author_sort | Chuanfang Wang |
| collection | DOAJ |
| description | Mild hypothermia has been proven to inhibit microglia activation after TBI. Exosomal microRNA derived from microglia played a critical role in promoting neurite outgrowth and synapse recovery. Here, we aimed to investigate the role of microRNAs in microglial exosomes after hypothermia treatment on neuronal regeneration after TBI. For in vitro study, stretch-injured neurons were co-cultured with microglial exosomes. For in vivo study, C57BL/6 mice were under controlled cortical impact and injected with microglial exosomes. The results showed that MG-LPS-EXOHT increased the number of dendrite branches and total length of dendrites both in vitro and in vivo, elevated the expression levels of PSD-95 and GluR1 in stretch-injured neurons, and increased spine density in the pericontusion region. Moreover, MG-LPS-EXOHT improved motor function and motor coordination. A high-throughput sequencing showed that miR-20b-5p was upregulated in MG-LPS-EXOHT. Elevating miR-20b-5p promoted neurite outgrowth and synapse recovery of injured neurons both in vitro and in vivo. Following mechanistic study demonstrated that miR-20b-5p might promote neurite outgrowth and synapse recovery by directly targeting PTEN and activating PI3K-AKT pathway. In conclusion, mild hypothermia could modify the microRNA prolife of exosomes derived from LPS activated BV2 cells. Furthermore, high level of microglial exosomal miR-20b-5p induced by mild hypothermia could transfer into injured neurons and promote neurite outgrowth and synapse recovery after TBI via activating the PI3K-AKT pathway by suppressing PTEN expression. |
| first_indexed | 2024-04-09T23:40:59Z |
| format | Article |
| id | doaj.art-da736a95f80d43e7967682c82edf9fc0 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-09T23:40:59Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-da736a95f80d43e7967682c82edf9fc02023-03-19T04:37:05ZengElsevierNeurobiology of Disease1095-953X2023-04-01179106042Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injuryChuanfang Wang0Yunxiang Ji1Huabin Zhang2Yongyi Ye3Guilong Zhang4Shizhen Zhang5Chengcheng Zhao6Yezhong Wang7Department of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, Guangdong, ChinaDepartment of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China; Corresponding author at: 78 Hengzhigang Road, Guangzhou, Guangdong, China.Department of Neurosurgery and Neurosurgical Disease Research Centre, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China; Corresponding author at: 250 Changgang East Road, Guangzhou, Guangdong, China.Mild hypothermia has been proven to inhibit microglia activation after TBI. Exosomal microRNA derived from microglia played a critical role in promoting neurite outgrowth and synapse recovery. Here, we aimed to investigate the role of microRNAs in microglial exosomes after hypothermia treatment on neuronal regeneration after TBI. For in vitro study, stretch-injured neurons were co-cultured with microglial exosomes. For in vivo study, C57BL/6 mice were under controlled cortical impact and injected with microglial exosomes. The results showed that MG-LPS-EXOHT increased the number of dendrite branches and total length of dendrites both in vitro and in vivo, elevated the expression levels of PSD-95 and GluR1 in stretch-injured neurons, and increased spine density in the pericontusion region. Moreover, MG-LPS-EXOHT improved motor function and motor coordination. A high-throughput sequencing showed that miR-20b-5p was upregulated in MG-LPS-EXOHT. Elevating miR-20b-5p promoted neurite outgrowth and synapse recovery of injured neurons both in vitro and in vivo. Following mechanistic study demonstrated that miR-20b-5p might promote neurite outgrowth and synapse recovery by directly targeting PTEN and activating PI3K-AKT pathway. In conclusion, mild hypothermia could modify the microRNA prolife of exosomes derived from LPS activated BV2 cells. Furthermore, high level of microglial exosomal miR-20b-5p induced by mild hypothermia could transfer into injured neurons and promote neurite outgrowth and synapse recovery after TBI via activating the PI3K-AKT pathway by suppressing PTEN expression.http://www.sciencedirect.com/science/article/pii/S0969996123000566ExosomesHypothermiaMicrogliaSynapseTraumatic brain injury |
| spellingShingle | Chuanfang Wang Yunxiang Ji Huabin Zhang Yongyi Ye Guilong Zhang Shizhen Zhang Chengcheng Zhao Yezhong Wang Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury Neurobiology of Disease Exosomes Hypothermia Microglia Synapse Traumatic brain injury |
| title | Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury |
| title_full | Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury |
| title_fullStr | Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury |
| title_full_unstemmed | Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury |
| title_short | Increased level of exosomal miR-20b-5p derived from hypothermia-treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury |
| title_sort | increased level of exosomal mir 20b 5p derived from hypothermia treated microglia promotes neurite outgrowth and synapse recovery after traumatic brain injury |
| topic | Exosomes Hypothermia Microglia Synapse Traumatic brain injury |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123000566 |
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