TY  - JOUR
AU  - Nörenberg, Dominik
AU  - Schmidt, Felix
AU  - Schinke, Karin
AU  - Frenzel, Thomas
AU  - Pietsch, Hubertus
AU  - Giese, Armin
AU  - Ertl-Wagner, Birgit
AU  - Levin, Johannes
TI  - Investigation of potential adverse central nervous system effects after long term oral administration of gadolinium in mice
JO  - PLOS ONE
VL  - 15
IS  - 4
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - DZNE-2020-01259
SP  - e0231495 -
PY  - 2020
AB  - 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.
KW  - Administration, Oral
KW  - Animals
KW  - Central Nervous System: drug effects
KW  - Female
KW  - Gadolinium: administration & dosage
KW  - Gadolinium: adverse effects
KW  - Locomotion: drug effects
KW  - Mice
KW  - Mice, Inbred C57BL
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC7179865
C6  - pmid:32324769
DO  - DOI:10.1371/journal.pone.0231495
UR  - https://pub.dzne.de/record/153262
ER  -