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Ceruloplasmin Deficiency Impaired Brain Iron Metabolism and Behavior in Mice

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Abstract

Iron accumulation is an important cause of various brain diseases. As a ferroxidase, ceruloplasmin (Cp) plays a key role in iron homeostasis and its abnormal activity leads to iron accumulation. However, the detailed biological function of Cp in brain iron homeostasis needs to be investigated. In this study, Cp knockout mice were prepared and the changes in iron content and protein expression related to iron metabolism were detected. The results showed that iron accumulation occurred in multiple tissues and organs of Cp knockout mice, but there was no obvious change in brain tissues. However, Cp deficiency affected the expression of many iron metabolism-related proteins in midbrain, such as DMT1+IRE, heavy chain ferritin (H-ferritin) and light chain ferritin (L-ferritin). Cp deficiency also impaired the behavioral ability of mice, including weakened exercise ability and reduced motor coordination. In vitro cell experiment indicated that the sensitivity of Cp knockout neuron and astrocyte to hypoxia was higher than that of wild type, which means Cp deficiency leads to the damage of cell self-protection. All these results confirm that Cp exerts a protective effect on the brain by regulating iron metabolism.

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Acknowledgements

The research was supported by Key R&D Program of Hebei Province (No. 18277752D).

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Authors and Affiliations

  1. Institute of Medicine, Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang, China

    Lijing Niu & Li Lu

  2. Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China

    Yi Zhou

  3. Department of Oncology, Hebei General Hospital, Shijiazhuang, China

    Aixia Su

  4. Department of Sport Human Sciences, Hebei Sport University, Shijiazhuang, China

    Xiaoqiang Guo

  5. Xiaobei Medical Research Institute, Department of Physical Education, Shijiazhuang Vocational College of Technology, Shijiazhuang, China

    Xiaoqiang Guo

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  1. Lijing Niu
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Contributions

L.N. and X.G. were responsible for experimental design, data analysis, and manuscript writing. L.N. conducted most of the experiments including tissue genotyping, iron content measurement, iron metabolism-related protein determination, behavioral tests, and in vitro cell experiment. Y.Z. assisted in behavioral experiment. L.L. was involved in the iron content measurement. A.S. was involved in data analysis and manuscript writing. All authors have read and approved the final manuscript.

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Correspondence to Lijing Niu or Xiaoqiang Guo.

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Niu, L., Zhou, Y., Lu, L. et al. Ceruloplasmin Deficiency Impaired Brain Iron Metabolism and Behavior in Mice. Cell Biochem Biophys 80, 385–393 (2022). https://doi.org/10.1007/s12013-022-01061-9

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