The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin

Peripherally-derived myeloid cells rapidly repopulate the microglia-depleted brain and adopt a microglia-like phenotype in wild type mice

To examine morphology and functionality of endogenous microglia and PDMCs in the non-diseased brain environment we crossed CX₃CR₁-GFP^+/− (Frac-GFP) males to CD11b-HSVTK^+/− (TK+) females. The resulting Frac-GFP;TK+ experimental mice were lethally irradiated and reconstituted intravenously with 10⁷ bone marrow (BM) cells isolated from ROSA26-tandem red fluorescent protein (tdRFP) reporter mice²⁷, to allow distinction of endogenous microglia (GFP-positive) and PDMCs (RFP-positive) with in vivo 2-photon imaging in the context of microglia depletion and myeloid cell repopulation. Four weeks after the BM transfer, microglia depletion was initiated by implanting a mini-osmotic pump (model 2001 cat.no. 0000292, Alzet) containing 2.5 mg Ganciclovir…