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DNA Methylation of the EphA5 Promoter Is Associated with Rat Congenital Hypothyroidism

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Abstract

Thyroid hormones (THs) are essential for normal development of the mammalian central nervous system through regulation of TH-responsive genes. EphA5, an important TH-responsive gene encoding the tyrosine kinase receptor EphA5, regulates synaptogenesis initiation and synaptic remodeling during brain development. Abnormal EphA5 expression is involved in the development of congenital hypothyroidism (CH). To show the regulatory mechanism of EphA5 expression in CH rats, we analyzed the correlation between methylation of the EphA5 promoter and its expression in the hypothyroid hippocampus and hippocampal neurons. Demethylation treatment using 5′-azadeoxycytidine upregulated EphA5 expression and rescued the effects of hypermethylation, suggesting a novel regulatory mechanism of EphA5 expression in CH rats. Our results suggest a potentially new approach for the development of drugs to restore neurocognitive impairments associated with CH.

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Acknowledgments

This study was supported by the Youth Fund of the National Natural Science Foundation of China (81201975), the Youth Fund of the Natural Science Foundation of Jiangsu Province (BK2012224), and the Six Major Human Resources Project of Jiangsu Province (2014-WSW-031).

Conflict of Interest

The authors declare that they have no competing interests.

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    Authors and Affiliations

    1. Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, Jiangsu Province, China

      Jinlong Shi

    2. Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China

      Youjia Wu, Honghua Song, Baolan Sun & Meiyu Xu

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    1. Youjia Wu
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    2. Honghua Song
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    3. Baolan Sun
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    Correspondence to Jinlong Shi.

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    Youjia Wu and Honghua Song contributed equally to this work.

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    Wu, Y., Song, H., Sun, B. et al. DNA Methylation of the EphA5 Promoter Is Associated with Rat Congenital Hypothyroidism. J Mol Neurosci 57, 203–210 (2015). https://doi.org/10.1007/s12031-015-0603-9

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    • DOI: https://doi.org/10.1007/s12031-015-0603-9

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