Academic Journal
The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner.
| العنوان: | The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner. |
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| المؤلفون: | Krisztina Tóth, Nikolett Lénárt, Péter Berki, Rebeka Fekete, Eszter Szabadits, Balázs Pósfai, Csaba Cserép, Ahmad Alatshan, Szilvia Benkő, Dániel Kiss, Christian A Hübner, Attila Gulyás, Kai Kaila, Zsuzsanna Környei, Ádám Dénes |
| المصدر: | PLoS Biology, Vol 20, Iss 1, p e3001526 (2022) |
| بيانات النشر: | Public Library of Science (PLoS), 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | Biology (General), QH301-705.5 |
| الوصف: | The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1β (IL-1β), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema and worse neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1544-9173 1545-7885 |
| Relation: | https://doaj.org/toc/1544-9173; https://doaj.org/toc/1545-7885 |
| DOI: | 10.1371/journal.pbio.3001526 |
| URL الوصول: | https://doaj.org/article/d912baf97e3f406590c12031ce06e71c |
| رقم الانضمام: | edsdoj.912baf97e3f406590c12031ce06e71c |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15449173 15457885 |
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| DOI: | 10.1371/journal.pbio.3001526 |