Abstract
Recent data suggest that ramified microglia fulfil various tasks in the brain. However, to investigate this unique cell type cultured primary microglia are only a poor model. We here describe a method to deplete and repopulate organotypic hippocampal slice cultures (OHSC) with ramified microglia isolated from adult mouse brain creating microglia-replenished OHSC (Mrep-OHSC). Replenished microglia integrate into the tissue and ramify to a degree indistinguishable from their counterparts in the mouse brain. Moreover, wild-type slices replenished with microglia from TNFα-deficient animals provide similar results as OHSC prepared from microglia-specific TNFα-knockout mice (CX3CR1(cre) /TNFα(fl/fl) ). Furthermore, this study demonstrates that replenished microglia in OHSC maintain original functions and properties acquired in vivo. Microglia from ERCC1(Δ/ko) mice, a mouse model of accelerated aging, maintain enhanced Mac2 expression and their activated phenotype after replenishment to wild-type OHSC tissue. Thus, the present study demonstrates that Mrep-OHSC are a unique tool to construct chimeric brain slices allowing studying the function of different phenotypes of in vivo like microglia in a tissue culture setting. GLIA 2016.
Original language | English |
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Pages (from-to) | 1285-1297 |
Number of pages | 13 |
Journal | Glia |
Volume | 64 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug-2016 |
Keywords
- hippocampus
- NMDA
- neuroprotection
- TNF alpha
- priming
- ERCC1
- HIPPOCAMPAL SLICE CULTURES
- CENTRAL-NERVOUS-SYSTEM
- TUMOR-NECROSIS-FACTOR
- DNA-REPAIR
- BRAIN
- CELLS
- INJURY
- MICE
- EXCITOTOXICITY
- NEURONS