Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome
Abstract Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflamma...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Biology Direct |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13062-023-00387-5 |
| _version_ | 1797801494066495488 |
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| author | Yaodan Zhang Yuyang Miao Xiangyang Xiong Jin Tan Zhaoli Han Fanglian Chen Ping Lei Qiang Zhang |
| author_facet | Yaodan Zhang Yuyang Miao Xiangyang Xiong Jin Tan Zhaoli Han Fanglian Chen Ping Lei Qiang Zhang |
| author_sort | Yaodan Zhang |
| collection | DOAJ |
| description | Abstract Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy. |
| first_indexed | 2024-03-13T04:51:19Z |
| format | Article |
| id | doaj.art-4132cf9a78da493fbb92542e9cdbe77c |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-03-13T04:51:19Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-4132cf9a78da493fbb92542e9cdbe77c2023-06-18T11:08:50ZengBMCBiology Direct1745-61502023-06-0118111810.1186/s13062-023-00387-5Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasomeYaodan Zhang0Yuyang Miao1Xiangyang Xiong2Jin Tan3Zhaoli Han4Fanglian Chen5Ping Lei6Qiang Zhang7Department of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalTianjin Medical UniversityDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalTianjin Neurological Institute, Tianjin Medical University General HospitalDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalDepartment of Geriatrics, Tianjin Geriatrics Institute, Tianjin Medical University General HospitalAbstract Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.https://doi.org/10.1186/s13062-023-00387-5Intermittent hypoxiaExosomesCognitionNLRP3 inflammationmiR-146a-5p |
| spellingShingle | Yaodan Zhang Yuyang Miao Xiangyang Xiong Jin Tan Zhaoli Han Fanglian Chen Ping Lei Qiang Zhang Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome Biology Direct Intermittent hypoxia Exosomes Cognition NLRP3 inflammation miR-146a-5p |
| title | Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome |
| title_full | Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome |
| title_fullStr | Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome |
| title_full_unstemmed | Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome |
| title_short | Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome |
| title_sort | microglial exosomes alleviate intermittent hypoxia induced cognitive deficits by suppressing nlrp3 inflammasome |
| topic | Intermittent hypoxia Exosomes Cognition NLRP3 inflammation miR-146a-5p |
| url | https://doi.org/10.1186/s13062-023-00387-5 |
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