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@ARTICLE{Eckenweber:153287,
      author       = {Eckenweber, Florian and Medina-Luque, Jose and Blume, Tanja
                      and Sacher, Christian and Biechele, Gloria and Wind, Karin
                      and Deussing, Maximilian and Briel, Nils and Lindner, Simon
                      and Boening, Guido and von Ungern-Sternberg, Barbara and
                      Unterrainer, Marcus and Albert, Nathalie L. and Zwergal,
                      Andreas and Levin, Johannes and Bartenstein, Peter and
                      Cumming, Paul and Rominger, Axel and Höglinger, Günter U.
                      and Herms, Jochen and Brendel, Matthias},
      title        = {{L}ongitudinal {TSPO} expression in tau transgenic
                      {P}301{S} mice predicts increased tau accumulation and
                      deteriorated spatial learning},
      journal      = {Journal of neuroinflammation},
      volume       = {17},
      number       = {1},
      issn         = {1742-2094},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2020-01284},
      pages        = {208},
      year         = {2020},
      abstract     = {BackgroundP301S tau transgenic mice show age-dependent
                      accumulation of neurofibrillary tangles in the brainstem,
                      hippocampus, and neocortex, leading to neuronal loss and
                      cognitive deterioration. However, there is hitherto only
                      sparse documentation of the role of neuroinflammation in tau
                      mouse models. Thus, we analyzed longitudinal microglial
                      activation by small animal 18 kDa translocator protein
                      positron-emission-tomography (TSPO μPET) imaging in vivo,
                      in conjunction with terminal assessment of tau pathology,
                      spatial learning, and cerebral glucose
                      metabolism.MethodsTransgenic P301S (n = 33) and wild-type (n
                      = 18) female mice were imaged by 18F-GE-180 TSPO μPET at
                      the ages of 1.9, 3.9, and 6.4 months. We conducted
                      behavioral testing in the Morris water maze,
                      18F-fluordesoxyglucose (18F-FDG) μPET, and AT8 tau
                      immunohistochemistry at 6.3–6.7 months. Terminal
                      microglial immunohistochemistry served for validation of
                      TSPO μPET results in vivo, applying target regions in the
                      brainstem, cortex, cerebellum, and hippocampus. We compared
                      the results with our historical data in amyloid-β mouse
                      models.ResultsTSPO expression in all target regions of P301S
                      mice increased exponentially from 1.9 to 6.4 months,
                      leading to significant differences in the contrasts with
                      wild-type mice at 6.4 months (+ $11–23\%,$ all p <
                      0.001), but the apparent microgliosis proceeded more slowly
                      than in our experience in amyloid-β mouse models. Spatial
                      learning and glucose metabolism of AT8-positive P301S mice
                      were significantly impaired at 6.3–6.5 months compared
                      to the wild-type group. Longitudinal increases in TSPO
                      expression predicted greater tau accumulation and lesser
                      spatial learning performance at
                      6.3–6.7 months.ConclusionsMonitoring of TSPO expression
                      as a surrogate of microglial activation in P301S tau
                      transgenic mice by μPET indicates a delayed time course
                      when compared to amyloid-β mouse models. Detrimental
                      associations of microglial activation with outcome
                      parameters are opposite to earlier data in amyloid-β mouse
                      models. The contribution of microglial response to pathology
                      accompanying amyloid-β and tau over-expression merits
                      further investigation.},
      cin          = {AG Herms / AG Levin / München common / AG Höglinger 1},
      ddc          = {610},
      cid          = {I:(DE-2719)1110001 / I:(DE-2719)1111016 /
                      I:(DE-2719)6000016 / I:(DE-2719)1110002},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
                      - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32660586},
      doi          = {10.1186/s12974-020-01883-5},
      url          = {https://pub.dzne.de/record/153287},
}