% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Kilzheimer:165137,
      author       = {Kilzheimer, Alexander and Hentrich, Thomas and Rotermund,
                      Carola and Kahle, Philipp J and Schulze-Hentrich, Julia M},
      title        = {{F}ailure of diet-induced transcriptional adaptations in
                      alpha-synuclein transgenic mice.},
      journal      = {Human molecular genetics},
      volume       = {32},
      number       = {3},
      issn         = {0964-6906},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DZNE-2022-01442},
      pages        = {450 - 461},
      year         = {2023},
      note         = {CC BY: https://creativecommons.org/licenses/by/4.0/},
      abstract     = {Nutritional influences have been discussed as potential
                      modulators of Parkinson's disease (PD) pathology through
                      various epidemiological and physiological studies. In animal
                      models, a high-fat diet (HFD) with greater intake of
                      lipid-derived calories leads to accelerated disease onset
                      and progression. The underlying molecular mechanisms of
                      HFD-induced aggravated pathology, however, remain largely
                      unclear. In this study, we aimed to further illuminate the
                      effects of a fat-enriched diet in PD by examining the
                      brainstem and hippocampal transcriptome of alpha-synuclein
                      transgenic mice exposed to a life-long HFD. Investigating
                      individual transcript isoforms, differential gene expression
                      and co-expression clusters, we observed that transcriptional
                      differences between wild-type (WT) and transgenic animals
                      intensified in both regions under HFD. Both brainstem and
                      hippocampus displayed strikingly similar transcriptomic
                      perturbation patterns. Interestingly, expression differences
                      resulted mainly from responses in WT animals to HFD, while
                      these genes remained largely unchanged or were even slightly
                      oppositely regulated by diet in transgenic animals. Genes
                      and co-expressed gene groups exhibiting this dysregulation
                      were linked to metabolic and mitochondrial pathways. Our
                      findings propose the failure of metabolic adaptions as the
                      potential explanation for accelerated disease unfolding
                      under exposure to HFD. From the identified clusters of
                      co-expressed genes, several candidates lend themselves to
                      further functional investigations.},
      keywords     = {Mice / Animals / Mice, Transgenic / alpha-Synuclein:
                      genetics / alpha-Synuclein: metabolism / Parkinson Disease:
                      genetics / Parkinson Disease: metabolism / Diet, High-Fat:
                      adverse effects / Gene Expression Profiling / Mice, Inbred
                      C57BL / alpha-Synuclein (NLM Chemicals)},
      cin          = {AG Kahle 2},
      ddc          = {570},
      cid          = {I:(DE-2719)1210000-4},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9851747},
      pubmed       = {pmid:36001352},
      doi          = {10.1093/hmg/ddac205},
      url          = {https://pub.dzne.de/record/165137},
}