| Autor: |
Morrison VE; Vanderbilt University Department of Biochemistry.; Vanderbilt Brain Institute.; Tulane University Center for Clinical Neuroscience Research., Houpert MG; Vanderbilt University Department of Biochemistry.; Vanderbilt Brain Institute., Trapani JB; Vanderbilt University Department of Biochemistry.; Vanderbilt Brain Institute., Brockman AA; Vanderbilt University Department of Cell and Developmental Biology.; Vanderbilt Brain Institute., Kingsley PJ; Vanderbilt University Department of Biochemistry., Katdare KA; Vanderbilt Brain Institute., Layden HM; Vanderbilt University Department of Biochemistry., Nguena-Jones G; Vanderbilt University Department of Biochemistry.; Vanderbilt Brain Institute., Trevisan AJ; Vanderbilt University Department of Biochemistry.; St. Jude Children's Research Hospital., Maguire-Zeiss KA; Georgetown University Department of Neuroscience., Marnett LJ; Vanderbilt University Department of Biochemistry.; Vanderbilt University Department of Chemistry.; Vanderbilt University Department of Pharmacology.; A.B. Hancock Jr. Memorial Laboratory for Cancer Research., Bix GJ; Tulane University Center for Clinical Neuroscience Research., Ihrie RA; Vanderbilt University Department of Cell and Developmental Biology.; Vanderbilt Brain Institute., Carter BD; Vanderbilt University Department of Biochemistry.; Vanderbilt Brain Institute. |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 06. Date of Electronic Publication: 2023 Mar 06. |
| DOI: |
10.1101/2023.03.03.531012 |
| Abstrakt: |
Microglia are the primary phagocytes in the central nervous system and are responsible for clearing dead cells generated during development or disease. The phagocytic process shapes the phenotype of the microglia, which affects the local environment. A unique population of microglia reside in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence this neurogenic niche is not well-understood. Here, we demonstrate that phagocytosis creates a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering the development of a neuroinflammatory phenotype, reminiscent of neurodegenerative and-age-associated microglia, that reduces neural precursor proliferation via elevated interleukin (IL)-1β signaling; inhibition of IL-1 receptor rescues precursor proliferation in vivo . Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to a phenotype that promotes neurogenesis in the developing V-SVZ. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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