| Summary: | Gadolinium deposition in the brain has been observed in areas rich in iron, such as the dentate nucleus of the cerebellum. We investigated the role of Fe<sup>2+</sup> in the effect of gadolinium-based contrast agents (GBCA) on thyroid hormone-mediated Purkinje cell dendritogenesis in a cerebellar primary culture. The study comprises the control group, Fe<sup>2+</sup> group, GBCA groups (gadopentetate group or gadobutrol group), and GBCA+Fe<sup>2+</sup> groups. Immunocytochemistry was performed with an anti-calbindin-28K (anti-CaBP28k) antibody, and the nucleus was stained with 4′,6-diamidino-2-phenylindole (DAPI). The number of Purkinje cells and their arborization were evaluated with an analysis of variance with a post-hoc test. The number of Purkinje cells was similar to the control groups among all treated groups. There were no significant differences in dendrite arborization between the Fe<sup>2+</sup> group and the control groups. The dendrite arborization was augmented in the gadopentetate and the gadobutrol groups when compared to the control group (<i>p</i> < 0.01, respectively). Fe<sup>2+</sup> significantly increased the effect of gadopentetate on dendrite arborization (<i>p</i> < 0.01) but did not increase the effect of gadobutrol. These findings suggested that the chelate thermodynamic stability and Fe<sup>2+</sup> may play important roles in attenuating the effect of GBCAs on the thyroid hormone-mediated dendritogenesis of Purkinje cells in in vitro settings.
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