TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis
Abstract Background Traumatic brain injury (TBI) is characterized by high mortality and disability rates. Disease-associated microglia (DAM) are a newly discovered subtype of microglia. However, their presence and function in the acute phase of TBI remain unclear. Although glycolysis is important fo...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-025-03337-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594588253028352 |
|---|---|
| author | Lin Wang Diqing Ouyang Lin Li Yunchuan Cao Yingwen Wang Nina Gu Zhaosi Zhang Zhao Li Shuang Tang Hui Tang Yuan Zhang Xiaochuan Sun Jin Yan |
| author_facet | Lin Wang Diqing Ouyang Lin Li Yunchuan Cao Yingwen Wang Nina Gu Zhaosi Zhang Zhao Li Shuang Tang Hui Tang Yuan Zhang Xiaochuan Sun Jin Yan |
| author_sort | Lin Wang |
| collection | DOAJ |
| description | Abstract Background Traumatic brain injury (TBI) is characterized by high mortality and disability rates. Disease-associated microglia (DAM) are a newly discovered subtype of microglia. However, their presence and function in the acute phase of TBI remain unclear. Although glycolysis is important for microglial differentiation, its regulatory role in DAM transformation during the acute phase of TBI is still unclear. In this study, we investigated the functions of DAM-like cells in the acute phase of TBI in mice, as well as the relationship between their transformation and glycolysis. Methods In this study, a controlled cortical impact model was used to induce TBI in adult male wild-type (WT) C57BL/6 mice and adult male TREM2 knockout mice. Various techniques were used to assess the role of DAM-like cells in TBI and the effects of glycolysis on DAM-like cells, including RT‒qPCR, immunofluorescence assays, behavioural tests, extracellular acidification rate (ECAR) tests, Western blot analysis, cell magnetic sorting and culture, glucose and lactate assays, and flow cytometry. Results DAM-like cells were observed in the acute phase of TBI in mice, and their transformation depended on TREM2 expression. TREM2 knockout impaired neurological recovery in TBI mice, possibly due in part to their role in clearing debris and secreting VEGFa and BDNF. Moreover, DAM-like cells exhibited significantly increased glycolytic activity. TREM2 regulated the AKT‒mTOR‒HIF-1α pathway and glycolysis in microglia in the acute phase of TBI. The increase in glycolysis in microglia partially contributed to the transformation of DAM-like cells in the acute phase of TBI in mice. Conclusions Taken together, the results of our study demonstrated that DAM-like cells were present in the acute phase of TBI in mice. TREM2 might influence DAM-like cell transformation by modulating the glycolysis of microglia. Our results provide a new possible pathway for intervening TBI. |
| format | Article |
| id | doaj-art-e9e6aa61802245879a9203b2b7535f7f |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-e9e6aa61802245879a9203b2b7535f7f2025-01-19T12:33:23ZengBMCJournal of Neuroinflammation1742-20942025-01-0122112610.1186/s12974-025-03337-2TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysisLin Wang0Diqing Ouyang1Lin Li2Yunchuan Cao3Yingwen Wang4Nina Gu5Zhaosi Zhang6Zhao Li7Shuang Tang8Hui Tang9Yuan Zhang10Xiaochuan Sun11Jin Yan12Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityEmergency Department, Chengdu First People’s HospitalDepartment of Neurosurgery, Suining Central HospitalDepartment of Neurosurgery, The Second Clinical Medical College of North Sichuan Medical College, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central HospitalDepartment of Neurosurgery, The Second Clinical Medical College of North Sichuan Medical College, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central HospitalDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Neurosurgery, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background Traumatic brain injury (TBI) is characterized by high mortality and disability rates. Disease-associated microglia (DAM) are a newly discovered subtype of microglia. However, their presence and function in the acute phase of TBI remain unclear. Although glycolysis is important for microglial differentiation, its regulatory role in DAM transformation during the acute phase of TBI is still unclear. In this study, we investigated the functions of DAM-like cells in the acute phase of TBI in mice, as well as the relationship between their transformation and glycolysis. Methods In this study, a controlled cortical impact model was used to induce TBI in adult male wild-type (WT) C57BL/6 mice and adult male TREM2 knockout mice. Various techniques were used to assess the role of DAM-like cells in TBI and the effects of glycolysis on DAM-like cells, including RT‒qPCR, immunofluorescence assays, behavioural tests, extracellular acidification rate (ECAR) tests, Western blot analysis, cell magnetic sorting and culture, glucose and lactate assays, and flow cytometry. Results DAM-like cells were observed in the acute phase of TBI in mice, and their transformation depended on TREM2 expression. TREM2 knockout impaired neurological recovery in TBI mice, possibly due in part to their role in clearing debris and secreting VEGFa and BDNF. Moreover, DAM-like cells exhibited significantly increased glycolytic activity. TREM2 regulated the AKT‒mTOR‒HIF-1α pathway and glycolysis in microglia in the acute phase of TBI. The increase in glycolysis in microglia partially contributed to the transformation of DAM-like cells in the acute phase of TBI in mice. Conclusions Taken together, the results of our study demonstrated that DAM-like cells were present in the acute phase of TBI in mice. TREM2 might influence DAM-like cell transformation by modulating the glycolysis of microglia. Our results provide a new possible pathway for intervening TBI.https://doi.org/10.1186/s12974-025-03337-2Traumatic brain injuryMicrogliaDisease-associated microgliaGlycolysisTriggering receptor expressed on myeloid cells 2 |
| spellingShingle | Lin Wang Diqing Ouyang Lin Li Yunchuan Cao Yingwen Wang Nina Gu Zhaosi Zhang Zhao Li Shuang Tang Hui Tang Yuan Zhang Xiaochuan Sun Jin Yan TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis Journal of Neuroinflammation Traumatic brain injury Microglia Disease-associated microglia Glycolysis Triggering receptor expressed on myeloid cells 2 |
| title | TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis |
| title_full | TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis |
| title_fullStr | TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis |
| title_full_unstemmed | TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis |
| title_short | TREM2 affects DAM-like cell transformation in the acute phase of TBI in mice by regulating microglial glycolysis |
| title_sort | trem2 affects dam like cell transformation in the acute phase of tbi in mice by regulating microglial glycolysis |
| topic | Traumatic brain injury Microglia Disease-associated microglia Glycolysis Triggering receptor expressed on myeloid cells 2 |
| url | https://doi.org/10.1186/s12974-025-03337-2 |
| work_keys_str_mv | AT linwang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT diqingouyang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT linli trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT yunchuancao trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT yingwenwang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT ninagu trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT zhaosizhang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT zhaoli trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT shuangtang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT huitang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT yuanzhang trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT xiaochuansun trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis AT jinyan trem2affectsdamlikecelltransformationintheacutephaseoftbiinmicebyregulatingmicroglialglycolysis |