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@ARTICLE{Strackeljan:276824,
      author       = {Strackeljan, Luisa and Baidoe-Ansah, David and
                      Mirzapourdelavar, Hadi and Jia, Shaobo and Kaushik, Rahul
                      and Cangalaya, Carla and Dityatev, Alexander},
      title        = {{P}artial microglial depletion through inhibition of
                      colony-stimulating factor 1 receptor improves synaptic
                      plasticity and cognitive performance in aged mice.},
      journal      = {Experimental neurology},
      volume       = {387},
      issn         = {0014-4886},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00337},
      pages        = {115186},
      year         = {2025},
      abstract     = {Microglia depletion, followed by repopulation, improves
                      cognitive functions in the aged mouse brain. However, even
                      temporal ablation of microglia puts the brain at a high risk
                      of infection. Hence, in the present work, we studied if the
                      partial reduction of microglia with PLX3397 (pexidartinib),
                      an inhibitor of the colony-stimulating factor 1 receptor
                      (CSF1R), could bring similar benefits as reported for
                      microglia ablation. Aged (two-years-old) mice were treated
                      with PLX3397 for a total of 6 weeks, which reduced microglia
                      numbers in the hippocampus and retrosplenial cortex (RSC) to
                      the levels seen in young mice and resulted in layer-specific
                      ablation in the expression of microglial complement protein
                      C1q mediating synaptic remodeling. This treatment boosted
                      long-term potentiation in the CA1 region and improved
                      performance in the hippocampus-dependent novel object
                      location recognition task. Although PLX3397 treatment did
                      not alter the number or total intensity of Wisteria
                      floribunda agglutinin-positive perineuronal nets (PNNs) in
                      the CA1 region of the hippocampus, it changed the fine
                      structure of PNNs. It also elevated the expression of
                      perisynaptic proteoglycan brevican, presynaptic vGluT1 at
                      excitatory synapses, and vGAT in inhibitory ones in the CA1
                      stratum radiatum. Thus, targeting the CSF1R may provide a
                      safe and efficient strategy to boost synaptic and cognitive
                      functions in the aged brain.},
      keywords     = {Aging (Other) / Brevican (Other) / Extracellular matrix
                      (Other) / Glia (Other) / Parvalbumin (Other) / Perineuronal
                      nets (Other) / Perisynaptic ECM (Other) / Synapses (Other)},
      cin          = {AG Dityatev},
      ddc          = {610},
      cid          = {I:(DE-2719)1310007},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39956381},
      doi          = {10.1016/j.expneurol.2025.115186},
      url          = {https://pub.dzne.de/record/276824},
}