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@PHDTHESIS{Mller:144807,
      author       = {Müller, Michaela},
      title        = {{NMDA} {R}eceptor-{D}ependent {A}myloid {B}eta {T}oxicity
                      in the {C}ontext of {A}lzheimer’s {D}isease},
      school       = {Ruprechts-Karls-Universität Heidelberg},
      type         = {Dissertation},
      reportid     = {DZNE-2020-00249},
      pages        = {101 pages, Ill.},
      year         = {2016},
      note         = {Dissertation, Ruprechts-Karls-Universität Heidelberg,
                      2016},
      abstract     = {The amyloid beta (Aβ) protein is known to mediate large
                      parts of the pathology seen in Alzheimer’s disease (AD).
                      Previous studies suggested that N-methyl-D-aspartate
                      receptors (NMDARs) mediate some of the Aβ toxicity.
                      However, it is not known in detail which NMDAR subunit plays
                      a role. In this study, I investigated the involvement of the
                      NMDAR subunits GluN1, GluN2A and GluN2B in Aβ toxicity by
                      genetically deleting single subunits in individual neurons
                      via injection of Cre-recombinase expressing AAVs into the
                      brain of adult mice in which the respective NMDAR genes were
                      flanked by loxP-sites (GluN1fl/fl, GluN2Afl/fl, and
                      GluN2Bfl/fl). Aβ toxicity was induced either short-term by
                      injection of AAVs overexpressing CT100(I716F) which leads to
                      increased Aβ42 production, or long-term by transgenic
                      overproduction in the 5xFAD mouse model. Both approaches
                      allowed me to demonstrate that NMDAR subunits are indeed
                      involved in Aβ toxicity in adult mice. Aβ induces a
                      decrease in functional synapse number which is prevented by
                      deletion of the GluN1 and GluN2B subunit and partially
                      prevented by deletion of the GluN2A subunit. Furthermore,
                      short-term Aβ overproduction induced an increase in spine
                      number which was prevented by GluN1 and Glu2A deletion.
                      Spine loss in the 5xFAD mouse line could be partially
                      rescued by GluN1 and GluN2B deletion. In summary, the
                      results of my thesis demonstrate the importance of both the
                      GluN2A and Glun2B subunit in Aβ toxicity and suggest that
                      AD treatment with NMDAR blockers might be beneficial when
                      treatment is started early.},
      cin          = {AG Engelhardt},
      cid          = {I:(DE-2719)1013023},
      pnm          = {341 - Molecular Signaling (POF3-341)},
      pid          = {G:(DE-HGF)POF3-341},
      typ          = {PUB:(DE-HGF)11},
      url          = {https://pub.dzne.de/record/144807},
}