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Effects of Excessive Iodine on the BDNF-TrkB Signaling Pathway and Related Genes in Offspring of EAT Rats

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Abstract

Excess iodine can cause autoimmune thyroiditis (AIT) in women, but it is unclear whether this has any implications for neurodevelopmental mechanisms in offspring. We studied the effects of experimental autoimmune thyroiditis (EAT) rats with different amounts of iodine intake on offspring brain development via the brain-derived neurotrophic factor (BDNF)-tropomycin receptor kinase B (TrkB) signaling pathway, because BDNF plays an important role in neurodevelopment. Rats in three thyroglobulin (Tg) immunized groups with varying iodine intakes (Tg (100 µg/L iodine), Tg + High-iodine I group (Tg + HI, 20 mg/L iodine), and Tg + High-iodine II group (Tg + HII, 200 mg/L iodine)) were injected with 800 µg Tg once every 2 weeks for 3 times. Rats in the control group (NI, 100 µg/L iodine) were immunized with saline. Arsenic-cerium catalytic spectrophotometry was used to measure urine iodine levels. The lymphocytic infiltration in the thyroids was observed by histopathological studies. Thyroid autoantibodies levels were measured using radioimmunoassay. The norepinephrine (NE) contents were measured by an enzyme-linked immunosorbent assay. The levels of the BDNF-TrkB signaling pathway and related genes were measured by quantitative real-time PCR and Western blot. Urinary iodine levels increased as iodine intake increased. Lymphocytes were significantly aggravated in Tg-immunized rats. Serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) levels were clearly elevated in Tg-immunized rats. Tg-immune groups had significantly lower NE levels. The BDNF-TrkB signaling pathway and related gene mRNA and protein levels were found to be significantly lower in Tg-immune groups with higher iodine levels. Maternal AIT may reduce the levels of certain neurodevelopmental mechanisms in the offspring, such as the BDNF-TrkB signaling pathway and related factors, while excessive iodine consumption by the mother may exacerbate this effect.

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Data Availability

Raw data from animals involved in this study will be kept confidential and will not be shared.

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Acknowledgements

We thank Prof. Hongmei Shen and Ms. Lixiang Liu and other researchers for their help, and the Key Laboratory of Pathogenesis and Epidemiology, Harbin Medical University (23618504) for providing experimental equipment and environment.

Funding

The study was supported by the National Natural Science Foundation of China (Grant No. 81703175).

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Authors and Affiliations

  1. Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin City, Heilongjiang Province, 150081, People’s Republic of China

    Meihui Jin, Zheng Zhou, Li Zhang, Yao Chen, Lixiang Liu & Hongmei Shen

  2. National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, China

    Meihui Jin, Zheng Zhou, Li Zhang, Yao Chen, Lixiang Liu & Hongmei Shen

  3. Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, China

    Meihui Jin, Zheng Zhou, Li Zhang, Yao Chen, Lixiang Liu & Hongmei Shen

Authors
  1. Meihui Jin
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  2. Zheng Zhou
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  3. Li Zhang
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  4. Yao Chen
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  5. Lixiang Liu
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  6. Hongmei Shen
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Contributions

Conceived and designed the experiments: Hongmei Shen, Lixiang Liu; Performed the experiments: Meihui Jin, Zheng Zhou, Li Zhang, Yao Chen; Established the mouse model: Meihui Jin, Zheng Zhou; Analyzed the data: Meihui Jin; Drafted the manuscript: Meihui Jin, Hongmei Shen, Lixiang Liu.

All authors reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Lixiang Liu or Hongmei Shen.

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Ethics Approval

The study was approved by the Medical Ethics Committee of the Endemic Disease Control Centre of Harbin Medical University (hrbmuecdc20170305) and complied with animal ethical requirements.

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The authors declare no competing interests.

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Jin, M., Zhou, Z., Zhang, L. et al. Effects of Excessive Iodine on the BDNF-TrkB Signaling Pathway and Related Genes in Offspring of EAT Rats. Biol Trace Elem Res 201, 776–785 (2023). https://doi.org/10.1007/s12011-022-03187-6

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  • DOI: https://doi.org/10.1007/s12011-022-03187-6

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