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@ARTICLE{Guenther:829465,
      author       = {Guenther, Anne and Luczak, Vince and Abel, Ted and Baumann,
                      Arnd},
      title        = {{C}aspase-3 and {GFAP} as early markers for apoptosis and
                      astrogliosis in sh{RNA}-induced hippocampal cytotoxicity},
      journal      = {The journal of experimental biology},
      volume       = {220},
      number       = {8},
      issn         = {1477-9145},
      address      = {Cambridge},
      reportid     = {FZJ-2017-03164},
      pages        = {1400 - 1404},
      year         = {2017},
      abstract     = {Genetic manipulation of cells and tissue by RNA
                      interference has significantly contributed to the functional
                      characterization of individual proteins and their role in
                      physiological processes. Despite its versatility, RNA
                      interference can have detrimental side effects, including
                      reduced cell viability. We applied recombinant
                      adeno-associated viruses by stereotaxic injection into the
                      murine hippocampus to express different short hairpin RNA
                      (shRNA) constructs along with eGFP. Tissue responses were
                      assessed immunohistochemically for up to 8 weeks
                      post-infection. Strong hippocampal degeneration and tissue
                      atrophy was observed, most likely induced by high shRNA
                      expression. The effect was entirely absent in mice injected
                      with vectors driving only expression of eGFP. Active
                      caspase-3 (Casp-3) and glial fibrillary acidic protein
                      (GFAP) were identified as molecular markers and early
                      indicators of adverse tissue responses. Our findings also
                      demonstrate that detrimental effects of high shRNA
                      expression in hippocampal tissue can be monitored even
                      before the onset of tissue degeneration.},
      cin          = {ICS-4},
      ddc          = {570},
      cid          = {I:(DE-Juel1)ICS-4-20110106},
      pnm          = {552 - Engineering Cell Function (POF3-552)},
      pid          = {G:(DE-HGF)POF3-552},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000399670800008},
      doi          = {10.1242/jeb.154583},
      url          = {https://juser.fz-juelich.de/record/829465},
}