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Contrasting Iron Metabolism in Undifferentiated Versus Differentiated MO3.13 Oligodendrocytes via IL-1β-Induced Iron Regulatory Protein 1

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Abstract

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of iron in the substantia nigra. While iron accumulation and inflammation are implicated in PD pathogenesis, their impact on oligodendrocytes, the brain’s myelin-forming cells, remains elusive. This study investigated the influence of interleukin-1β (IL-1β), an elevated proinflammatory cytokine in PD, on iron-related proteins in MO3.13 oligodendrocytes. We found that IL-1β treatment in undifferentiated MO3.13 oligodendrocytes increased iron regulatory protein 1 and transferrin receptor 1 (TfR1) expression while decreasing ferroportin 1 (FPN1) expression. Consequently, iron uptake was enhanced, and iron release was reduced, leading to intracellular iron accumulation. Conversely, IL-1β treatment in differentiated MO3.13 oligodendrocytes exhibited the opposite effect, with decreased TfR1 expression, increased FPN1 expression, and reduced iron uptake. These findings suggest that IL-1β-induced dysregulation of iron metabolism in oligodendrocytes may contribute to the pathological processes observed in PD. IL-1β can increase the iron content in undifferentiated oligodendrocytes, thus facilitating the differentiation of undifferentiated MO3.13 oligodendrocytes. In differentiated oligodendrocytes, IL-1β may facilitate iron release, providing a potential source of iron for neighboring dopaminergic neurons, thereby initiating a cascade of deleterious events. This study provides valuable insights into the intricate interplay between inflammation, abnormal iron accumulation, and oligodendrocyte dysfunction in PD. Targeting the IL-1β-mediated alterations in iron metabolism may hold therapeutic potential for mitigating neurodegeneration and preserving dopaminergic function in PD.

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All data analyzed in this study are included within the article.

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Acknowledgements

This work was supported by Grants from the National Natural Science Foundation of China (31571054), Shandong Provincial Key Research and Development Project (2019GSF108224), Natural Science Foundation of Shandong Province (ZR2021MC116).

Funding

This study was funded by the Natural Science Foundation of Shandong Province (ZR2021MC116), National Natural Science Foundation of China (31571054), Shandong Provincial Key Research and Development Project (2019GSF108224).

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  1. Jiahua Yang and Chenchen Du are co-first authors.

Authors and Affiliations

  1. School of Basic Medicine, Qingdao University, Qingdao, 266071, China

    Jiahua Yang, Chenchen Du, Yinghui Li, Rong Liu, Cuiting **g & Jun Wang

  2. Institute of Brain Science and Disease, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao, 266071, China

    Junxia **e & Jun Wang

  3. Institute of Senior Care and Art, Guangdong Vocational College of Hotel Management, Dongguan, China

    Chenchen Du

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Contributions

JW and JX: designed the study and revised the manuscript. JY: wrote the manuscript. CD and YL: performed experiments and analyzed the data. RL and CJ: assisted with experimental techniques, analyzed the data.

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Correspondence to Jun Wang.

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Yang, J., Du, C., Li, Y. et al. Contrasting Iron Metabolism in Undifferentiated Versus Differentiated MO3.13 Oligodendrocytes via IL-1β-Induced Iron Regulatory Protein 1. Neurochem Res 49, 466–476 (2024). https://doi.org/10.1007/s11064-023-04047-y

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