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@ARTICLE{Nrenberg:153262,
      author       = {Nörenberg, Dominik and Schmidt, Felix and Schinke, Karin
                      and Frenzel, Thomas and Pietsch, Hubertus and Giese, Armin
                      and Ertl-Wagner, Birgit and Levin, Johannes},
      title        = {{I}nvestigation of potential adverse central nervous system
                      effects after long term oral administration of gadolinium in
                      mice},
      journal      = {PLOS ONE},
      volume       = {15},
      number       = {4},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DZNE-2020-01259},
      pages        = {e0231495 -},
      year         = {2020},
      abstract     = {ObjectivesTo examine potential gadolinium (Gd) accumulation
                      in the brain of healthy mice after long-term oral
                      administration of Gd-containing food pellets and to
                      investigate whether Gd leads to adverse central nervous
                      system (CNS) effects, specifically focussing on locomotor
                      impairment in Gd exposed compared to control
                      animals.Materials and methodsThe local Animal Experimental
                      Ethics Committee approved all procedures and applications.
                      Fifteen female C57Bl/6 mice were orally exposed to a daily
                      intake of 0.57 mmol Gd chloride/ kg body weight over a
                      period of 90 weeks from the age of 4 weeks on. Gd-free, but
                      otherwise equivalent experimental diets were given to the
                      control group (N = 13). The animals were monitored daily by
                      animal caretakers regarding any visible signs of distress
                      and evaluated clinically every four weeks for the first 60
                      weeks and afterwards every two weeks for a better temporal
                      resolution of potential long-term effects regarding
                      impairment of motor performance and loss of body weight. The
                      individual Gd content was measured using mass spectrometry
                      in a sub-cohort of N = 6 mice.ResultsThe absolute brain Gd
                      levels of the Gd-exposed mice were significantly increased
                      compared to control mice (0.033± 0.009 vs. 0.006± 0.002
                      nmol Gd/ g brain tissue). Long-term oral Gd exposure over
                      almost the entire life-span did not lead to adverse CNS
                      effects including locomotor changes (rotarod performance, p
                      = 0.1467) in healthy mice throughout the study period.
                      Gd-exposed mice showed less increased body weight compared
                      to control mice during the study period (p = 0.0423).
                      Histopathological alterations, such as hepatocellular
                      vacuolization due to fatty change in the liver and a loss of
                      nucleated cells in the red pulp of the spleen, were found in
                      peripheral organs of both groups.ConclusionsLow levels of
                      intracerebral Gd caused by chronic oral exposure over almost
                      the entire life span of mice did not lead to alterations in
                      locomotor abilities in healthy mice throughout the normal
                      aging process.},
      keywords     = {Administration, Oral / Animals / Central Nervous System:
                      drug effects / Female / Gadolinium: administration $\&$
                      dosage / Gadolinium: adverse effects / Locomotion: drug
                      effects / Mice / Mice, Inbred C57BL},
      cin          = {München Pre 2020 / Clinical Dementia Research München},
      ddc          = {610},
      cid          = {I:(DE-2719)6000016 / I:(DE-2719)1111016},
      pnm          = {344 - Clinical and Health Care Research (POF3-344)},
      pid          = {G:(DE-HGF)POF3-344},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC7179865},
      pubmed       = {pmid:32324769},
      doi          = {10.1371/journal.pone.0231495},
      url          = {https://pub.dzne.de/record/153262},
}