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Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration
Published on: June 18, 2018
Effects of Gadolinium Deposition in the Brain on Motor or Behavioral Function: A Mouse Model
Hiroyuki Akai1, Kazuya Miyagawa1, Kohei Takahashi1
1From the Department of Radiology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan (H.A., H.S., K.Y., A.K.); Department of Pharmacology, and School of Pharmacy (K.M., K.T., A.M.S., K.K., M.T.), and International University of Health and Welfare (K.O.), Ohtawara, Tochigi, Japan; Department of Pharmacology, School of Pharmacy at Fukuoka, International University of Health and Welfare, Okawa, Fukuoka, Japan (H.T.); Department of Diagnostic Radiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan (Y.I.); Department of Radiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan (O.A.); and Department of Radiology, International University of Health and Welfare, Narita, Chiba, Japan (S.K.).
Abstract:
Background Recent studies showing gadolinium deposition in multiple organs have raised concerns about the safety of gadolinium-based contrast agents (GBCAs). Purpose To explore whether gadolinium deposition in brain structures will cause any motor or behavioral alterations. Materials and Methods This study was performed from July 2019 to December 2020. Groups of 17 female BALB/c mice were each repeatedly injected with phosphate-buffered saline (control group, group A), a macrocyclic GBCA (group B), or a linear GBCA (group C) for 8 weeks (5 mmol per kilogram of bodyweight per week for GBCAs). Brain MRI studies were performed every other week to observe the signal intensity change caused by the gadolinium deposition. After the injection period, rotarod performance test, open field test, elevated plus-maze test, light-dark anxiety test, locomotor activity assessment test, passive avoidance memory test, Y-maze test, and forced swimming test were performed to assess the locomotor abilities, anxiety level, and memory. Among-group differences were compared by using one-way or two-way factorial analysis of variance with Tukey post hoc testing or Dunnett post hoc testing. Results Gadolinium deposition in the bilateral deep cerebellar nuclei was confirmed with MRI only in mice injected with a linear GBCA. At 8 weeks, contrast ratio of group C (0.11; 95% CI: 0.10, 0.12) was higher than that of group A (-2.1 × 10-3; 95% CI: -0.011, 7.5 × 10-3; P < .001) and group B (2.7 × 10-4; 95% CI: -8.2 × 10-3, 8.7 × 10-3; P < .001). Behavioral analyses showed that locomotor abilities, anxiety level, and long-term or short-term memory were not different in mice injected with linear or macrocyclic GBCAs. Conclusion No motor or behavioral alterations were observed in mice with brain gadolinium deposition. Also, the findings support the safety of macrocyclic gadolinium-based contrast agents. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Chen in this issue.

