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@ARTICLE{Wassouf:141683,
      author       = {Wassouf, Zinah and Hentrich, Thomas and Samer, Sebastian
                      and Rotermund, Carola and Kahle, Philipp J and Ehrlich,
                      Ingrid and Riess, Olaf and Casadei, Nicolas and
                      Schulze-Hentrich, Julia M},
      title        = {{E}nvironmental {E}nrichment {P}revents {T}ranscriptional
                      {D}isturbances {I}nduced by {A}lpha-{S}ynuclein
                      {O}verexpression.},
      journal      = {Frontiers in cellular neuroscience},
      volume       = {12},
      issn         = {1662-5102},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {DZNE-2020-00014},
      pages        = {112},
      year         = {2018},
      abstract     = {Onset and progression of neurodegenerative disorders,
                      including synucleinopathies such as Parkinson's disease,
                      have been associated with various environmental factors. A
                      highly compelling association from a therapeutic point of
                      view has been found between a physically active lifestyle
                      and a significantly reduced risk for Parkinson's disease.
                      Mimicking such conditions in animal models by promoting
                      physical activity, social interactions, and novel
                      surroundings yields in a so-called enriched environment
                      known to enhance adult neurogenesis, increase synaptic
                      plasticity, and decelerate neuronal loss. Yet, the genes
                      that connect beneficial environmental cues to the genome and
                      delay disease-related symptoms have remained largely
                      unclear. To identify such mediator genes, we used a 2 × 2
                      factorial design opposing genotype and environment.
                      Specifically, we compared wildtype to transgenic mice
                      overexpressing human SNCA, a key gene in synucleinopathies
                      encoding alpha-synuclein, and housed them in a standard and
                      enriched environment from weaning to 12 months of age before
                      profiling their hippocampal transcriptome using
                      RNA-sequencing. Under standard environmental conditions,
                      differentially expressed genes were overrepresented for
                      calcium ion binding, membrane, synapse, and other Gene
                      Ontology terms previously linked to alpha-synuclein biology.
                      Upregulated genes were significantly enriched for genes
                      attributed to astrocytes, microglia, and oligodendrocytes.
                      These disturbances in gene activity were accompanied by
                      reduced levels of several presynaptic proteins and the
                      immediate early genes EGR1 and NURR1. Intriguingly, housing
                      transgenic animals in the enriched environment prevented
                      most of these perturbations in gene activity. In addition, a
                      sustained activation specifically in transgenic animals
                      housed in enriched conditions was observed for several
                      immediate early genes including Egr1, Nr4a2/Nurr1, Arc, and
                      Homer1a. These findings suggest a compensatory mechanism
                      through an enriched environment-activated immediate early
                      gene network that prevented most disturbances induced by
                      alpha-synuclein overexpression. This regulatory framework
                      might harbor attractive targets for novel therapeutic
                      approaches that mimic beneficial environmental stimuli.},
      cin          = {AG Kahle 2},
      ddc          = {610},
      cid          = {I:(DE-2719)1210000-4},
      pnm          = {899H - Addenda (POF3-899H)},
      pid          = {G:(DE-HGF)POF3-899H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29755323},
      pmc          = {pmc:PMC5932345},
      doi          = {10.3389/fncel.2018.00112},
      url          = {https://pub.dzne.de/record/141683},
}