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Marginal Iodine Deficiency Affects Dendritic Spine Development by Disturbing the Function of Rac1 Signaling Pathway on Cytoskeleton

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Abstract

Iodine deficiency (ID)-induced thyroid hormone (TH) insufficient during development leads to impairments of brain function, such as learning and memory. Marginal ID has been defined as subtle insufficiency of TH, characterized as low thyroxine (T4) levels, whether marginal ID potentially had adverse effects on the development of hippocampus and the underlying mechanisms remain unclear. Thus, in the present study, we established Wistar rat models with ID diet during pregnancy and lactation. The effects of marginal ID on long-term potentiation (LTP) were investigated in the hippocampal CA1 region. To study the development of dendritic spines in pyramidal cells, Golgi-Cox staining was conducted on postnatal day (PN) 7, PN14, PN21, and PN28. The activation of Rac1 signaling pathway, which is essential for dendritic spine development by regulating actin cytoskeleton, was also investigated. Our results showed that marginal ID slightly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Besides, the density of dendritic spines during the critical period of rat postnatal development was mildly decreased, and we found no significant change of spine morphology in marginal ID group. We also observed decreased activation of the Rac1 signaling pathway in pups subjected to maternal marginal ID. Our study may support the hypothesis that decreased T4 induced by marginal ID results in slight impairments of LTP and leads to mild damage of dendritic spine development, which may be due to abnormal regulation of Rac1 signaling pathway on cytoskeleton.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant numbers 81102126), Important Platform of Science and Technology for the Universities in Liaoning Province (grant number 16010), and Program for Liaoning Innovative Research Team in University (grant number LT2015028).

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Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People’s Republic of China

    Hui Min, Jing Dong, Yi Wang, Yuan Wang, Ye Yu & Jie Chen

  2. Liaoning Provincial Key Laboratory of Endocrine Diseases, the First Hospital of China Medical University, Shenyang, People’s Republic of China

    Zhongyan Shan & Weiping Teng

  3. Department of Physiology, the University of Tennessee Health Science Center, Memphis, TN, 38163, USA

    Qi Xi

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  1. Hui Min
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Correspondence to Jie Chen.

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Min, H., Dong, J., Wang, Y. et al. Marginal Iodine Deficiency Affects Dendritic Spine Development by Disturbing the Function of Rac1 Signaling Pathway on Cytoskeleton. Mol Neurobiol 54, 437–449 (2017). https://doi.org/10.1007/s12035-015-9657-5

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