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Effect of thyroxine on synaptotagmin 1 and SNAP-25 expression in dorsal hippocampus of adult-onset hypothyroid rats

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Abstract

Adult-onset hypothyroidism causes cognitive dysfunctions of learning and memory, in which many synaptic proteins in hippocampus are involved. In our work, we studied the effect of adult-onset hypothyroidism on the expression of synaptotagmin 1 (syt 1) and SNAP-25 in dorsal hippocampus as well as its recovery by levothyroxine (L-T4) replacement therapy. Rats were divided into 4 groups: control, hypothyroidism, and hypothyroid rats treated with 5 μg T4/100 g body weight (BW) and 20 μg L-T4/100 g BW, respectively. Protein levels of syt 1 and SNAP-25 in dorsal hippocampus were determined by Western blot and immuno-histochemistry. The immunoblot analysis indicated that syt 1 was expressed at a significantly lower level in hypothyroid rats, while the level of SNAP-25 was much higher compared to controls. Furthermore, using immunostaining, we found that on the one hand, expression of syt 1 was significantly down-regulated in the examined layers of CA1 and CA3 sub-regions but not dentate gyrus (DG); however, on the other hand, expression of SNAP-25 was up-regulated in the layers of CA1, CA3, and DG. Two-week treatment with 20 μg L-T4/100 g BW fully restored the levels of syt 1 and SNAP-25 to the normal level, which was more effective than 5 μg L-T4/100 g BW that partially restored the levels of both proteins. These results suggest that adult-onset hypothyroidism caused down-regulation of syt 1 and up-regulation of SNAP-25 level in dorsal hippocampus, which could be restored by L-T4 treatment, and the recovery degree is related to the L-T4 dosage.

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Authors and Affiliations

  1. Department of Endocrinology, Anhui Geriatric Institute, the First Affiliated Hospital, China

    C. L. Liu, Y. X. Xu, Y. Zhan, H. L. Hu & D. F. Zhu MD

  2. Comprehensive laboratory, College of Basic Medicine, China

    X. M. Jia

  3. Department of Neurology, Anhui Geriatric Institute, the First Affiliated Hospital, Anhui Medical University, Anhui, China

    G. H. Chen

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  1. C. L. Liu
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  2. Y. X. Xu
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  3. Y. Zhan
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  4. H. L. Hu
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  5. X. M. Jia
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  6. G. H. Chen
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  7. D. F. Zhu MD
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Correspondence to D. F. Zhu MD.

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C.L. Liu and Y.X. Xu contributed to this work equally

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Liu, C.L., Xu, Y.X., Zhan, Y. et al. Effect of thyroxine on synaptotagmin 1 and SNAP-25 expression in dorsal hippocampus of adult-onset hypothyroid rats. J Endocrinol Invest 34, 280–286 (2011). https://doi.org/10.1007/BF03347086

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  • DOI: https://doi.org/10.1007/BF03347086

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