Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice
Abstract Microglia are critically involved in post‐stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro‐inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. Ho...
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202306863 |
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| author | Wei Wei Seyed Siyawasch Justus Lattau Wenqiang Xin Yongli Pan Lars Tatenhorst Lin Zhang Irina Graf Yaoyun Kuang Xuan Zheng Zhongnan Hao Aurel Popa‐Wagner Stefan T. Gerner Sabine Huber Manuel Nietert Christian Klose Ertugrul Kilic Dirk M. Hermann Mathias Bähr Hagen B. Huttner Hua Liu Dirk Fitzner Thorsten R. Doeppner |
| author_facet | Wei Wei Seyed Siyawasch Justus Lattau Wenqiang Xin Yongli Pan Lars Tatenhorst Lin Zhang Irina Graf Yaoyun Kuang Xuan Zheng Zhongnan Hao Aurel Popa‐Wagner Stefan T. Gerner Sabine Huber Manuel Nietert Christian Klose Ertugrul Kilic Dirk M. Hermann Mathias Bähr Hagen B. Huttner Hua Liu Dirk Fitzner Thorsten R. Doeppner |
| author_sort | Wei Wei |
| collection | DOAJ |
| description | Abstract Microglia are critically involved in post‐stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro‐inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD‐rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post‐stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF‐α, IL‐6, and IL‐1β as well as a pro‐inflammatory phenotype and differentially expressed lipid metabolism‐related genes. These post‐ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post‐ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury. |
| format | Article |
| id | doaj-art-023492e079da4284ab33fb3a61b03e15 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-023492e079da4284ab33fb3a61b03e152025-08-20T02:12:24ZengWileyAdvanced Science2198-38442024-11-011141n/an/a10.1002/advs.202306863Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in MiceWei Wei0Seyed Siyawasch Justus Lattau1Wenqiang Xin2Yongli Pan3Lars Tatenhorst4Lin Zhang5Irina Graf6Yaoyun Kuang7Xuan Zheng8Zhongnan Hao9Aurel Popa‐Wagner10Stefan T. Gerner11Sabine Huber12Manuel Nietert13Christian Klose14Ertugrul Kilic15Dirk M. Hermann16Mathias Bähr17Hagen B. Huttner18Hua Liu19Dirk Fitzner20Thorsten R. Doeppner21Department of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Hospital Essen University of Duisburg‐Essen 45147 Essen GermanyDepartment of Neurology University of Giessen Medical School 35392 Giessen GermanyDepartment of Neurology University of Giessen Medical School 35392 Giessen GermanyDepartment of Medical Bioinformatics UMG University of Göttingen 37075 Göttingen GermanyLipotype GmbH 01307 Dresden GermanyDepartment of Physiology Faculty of Medicine Istanbul Medeniyet University Istanbul 34720 TurkeyDepartment of Neurology University Hospital Essen University of Duisburg‐Essen 45147 Essen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University of Giessen Medical School 35392 Giessen GermanyDepartment of Neurology The Affiliated Hospital of Southwest Jiaotong University & The Third People's Hospital of Chengdu ChengduSichuan 610031 ChinaDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyDepartment of Neurology University Medicine Göttingen (UMG) University of Göttingen 37075 Göttingen GermanyAbstract Microglia are critically involved in post‐stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro‐inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD‐rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post‐stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF‐α, IL‐6, and IL‐1β as well as a pro‐inflammatory phenotype and differentially expressed lipid metabolism‐related genes. These post‐ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post‐ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.https://doi.org/10.1002/advs.202306863cholesterol metabolismischemic strokelipid dropletslipid metabolismlipidomicsmicroglia |
| spellingShingle | Wei Wei Seyed Siyawasch Justus Lattau Wenqiang Xin Yongli Pan Lars Tatenhorst Lin Zhang Irina Graf Yaoyun Kuang Xuan Zheng Zhongnan Hao Aurel Popa‐Wagner Stefan T. Gerner Sabine Huber Manuel Nietert Christian Klose Ertugrul Kilic Dirk M. Hermann Mathias Bähr Hagen B. Huttner Hua Liu Dirk Fitzner Thorsten R. Doeppner Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice Advanced Science cholesterol metabolism ischemic stroke lipid droplets lipid metabolism lipidomics microglia |
| title | Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice |
| title_full | Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice |
| title_fullStr | Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice |
| title_full_unstemmed | Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice |
| title_short | Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice |
| title_sort | dynamic brain lipid profiles modulate microglial lipid droplet accumulation and inflammation under ischemic conditions in mice |
| topic | cholesterol metabolism ischemic stroke lipid droplets lipid metabolism lipidomics microglia |
| url | https://doi.org/10.1002/advs.202306863 |
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