Affiliations: [a] Department of Neurology, University of Rostock, Neurodegeneration Research Lab (NRL), Germany
| [b] Department of Neuro-/Pathology, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway
| [c]
University of Lübeck (UzL), LIED, Lübeck, Germany
| [d] Department of Pharmacology, University of Latvia, Rīga, Latvia
Correspondence:
[*]
Correspondence to: Jens Pahnke, University of Oslo, Department of Pathology (PAT), Translational Neurodegeneration Research and Neuropathology Lab, Postboks 4950 Nydalen, 0424 Oslo, Norway. Tel.: +47 230 71466; E-mail: [email protected].
Note: [1
] These authors contributed equally to this work.
Note: [2
] Current address: Core Facility Multimodal Small Animal Imaging, University of Rostock, Germany.
Abstract: Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer’s disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging. To study the impact of mitochondrial alterations on microglial activity in a homogeneous genetic background, we generated bone marrow chimeras of irradiated 46-days-old APP-transgenic mice. For reconstitution, bone marrow from CX3CR1-eGFP mice with mitochondria of either non-obese diabetic or C57BL/6J animals was utilized. Successful reconstitution was evident in 100-day-old animals, by the presence of eGFP-positive cells in liver and spleen. In the brain, one-third of IBA1-positive microglia cells were newly recruited eGFP-expressing cells. Although donor-derived microglia were equally located in the proximity of amyloid plaques, no difference was observed in either the amyloid level, total number, or microglial coverage of plaques. These results indicate that during this brief and early phase of amyloid deposition, beneficial mitochondrial alterations in the newly recruited third of microglial cells were not sufficient to affect the amyloidosis in APP-transgenic mice.
