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@ARTICLE{Khan:294721,
      author       = {D. Khan and D. Bock$^*$ and H.-K. Liu$^*$ and S. Muhammad},
      title        = {{T}lx {P}romotes {S}troke-{I}nduced {N}eurogenesis and
                      {N}euronal {R}epair in {Y}oung and {A}ged {M}ice.},
      journal      = {International journal of molecular sciences},
      volume       = {25},
      number       = {22},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DKFZ-2024-02454},
      pages        = {12440},
      year         = {2024},
      note         = {DKFZ-ZMBH Alliance},
      abstract     = {Stroke is one of the leading causes of chronic disability
                      in humans. It has been proposed that the endogenous neural
                      stem/progenitor cells generate new neurons in the damaged
                      area. Still, the contribution of these cells is negligible
                      because a low number of newborn mature neurons are formed.
                      Tlx conventional knock-out mice, Tlx-CreERT2 mice, and
                      Tlx-overexpressing (Tlx-OE) mice were specifically chosen
                      for their unique genetic characteristics, which were crucial
                      for the experiments. Permanent and transient middle cerebral
                      artery occlusion was used to induce stroke in the mice.
                      Immunostainings for doublecortin and GFP/BrdU/NeuN were
                      performed to study neurogenesis and fate mapping. The
                      rotarod test was performed to assess motor deficits. Here,
                      we show that stroke-induced neurogenesis is dramatically
                      increased with the additional expression of two copies of
                      the nuclear receptor-coding gene tailless (Tlx, also known
                      as Nr2e1), which has been shown to be a master regulator of
                      subventricular zone (SVZ) neural stem cells (NSCs). We show
                      that Tlx expression is upregulated after stroke, and
                      stroke-induced neurogenesis is blocked when Tlx is
                      inactivated. Tlx overexpression in NSCs leads to massive
                      induction of neurogenesis via stroke. More newborn mature
                      neurons are formed in Tlx-overexpressing mice, leading to
                      improved coordination and motor function recovery. Most
                      importantly, we also demonstrate that this process is
                      sustained in aged mice, where stroke-induced neurogenesis is
                      nearly undetectable in wild-type animals. This study
                      provides the first stem cell-specific genetic evidence that
                      endogenous NSCs can be exploited by manipulating their
                      master regulator, Tlx, and thus suggests a novel therapeutic
                      strategy for neuronal repair.},
      keywords     = {Animals / Neurogenesis / Mice / Neural Stem Cells:
                      metabolism / Neural Stem Cells: cytology / Stroke:
                      metabolism / Stroke: pathology / Neurons: metabolism /
                      Receptors, Cytoplasmic and Nuclear: metabolism / Receptors,
                      Cytoplasmic and Nuclear: genetics / Aging: metabolism /
                      Mice, Knockout / Male / Mice, Inbred C57BL / Infarction,
                      Middle Cerebral Artery: metabolism / Infarction, Middle
                      Cerebral Artery: pathology / Tlx (Other) / adult
                      neurogenesis (Other) / neural stem cells (Other) / stroke
                      (Other) / Nr2e1 protein, mouse (NLM Chemicals) / Receptors,
                      Cytoplasmic and Nuclear (NLM Chemicals)},
      cin          = {W190 / A240},
      ddc          = {540},
      cid          = {I:(DE-He78)W190-20160331 / I:(DE-He78)A240-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39596503},
      pmc          = {pmc:PMC11594625},
      doi          = {10.3390/ijms252212440},
      url          = {https://inrepo02.dkfz.de/record/294721},
}