Open Access

Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats

  • Authors:
    • Fen Wang
    • Zhangbi Wu
    • Xiaoxue Zha
    • Yaojun Cai
    • Bo Wu
    • Xuemei Jia
    • Defa Zhu
  • View Affiliations

  • Published online on: July 14, 2017     https://doi.org/10.3892/mmr.2017.6977
  • Pages: 3233-3241
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to observe the effects of the concurrent administration of thyroxine (T4) and an acetylcholinesterase (AChE) inhibitor, donepezil (DON), on the hypothyroidism‑induced ultrastructural changes of the prefrontal cortex (PFC) in adult rats. The acetylcholine (ACh) content and AChE activity was assessed, as well as the expressions of synaptotagmin‑1 (syt‑1) and SNAP‑25 were analyzed in the rats. Adding 0.05% propylthiouracil to rats' drinking water induced a hypothyroid rat model. The animals were treated with T4 and DON administered separately or in combination from the fifth week. Transmission electron microscope analysis revealed that hypothyroidism induced marked ultrastructural changes, including the neurons, the synapses and the myelin sheath in the PFC. T4 or DON treatment improved the morphologic features of the PFC, and the performance of the T4 combined DON group was the closest to the control group. Moreover, hypothyroidism significantly decreased the content of ACh (29.8%) and activity of AChE (27.8%), which were restored to control values by T4 admi­nistration. In addition, DON treatment restored ACh content to normal. At the protein level, hypothyroidism increased the levels of syt‑1 and SNAP‑25 in the PFC, both of which were not restored to control values following T4 administration, while concurrent administration of T4 and DON was able to induce this effect. These results suggested that adult‑onset hypothyroidism induce morphological, biochemical and molecular alterations in the PFC, combined administration of T4 and DON induce plastic changes in the PFC, different from that of the standard T4 therapy, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.
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September-2017
Volume 16 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang F, Wu Z, Zha X, Cai Y, Wu B, Jia X and Zhu D: Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats. Mol Med Rep 16: 3233-3241, 2017
APA
Wang, F., Wu, Z., Zha, X., Cai, Y., Wu, B., Jia, X., & Zhu, D. (2017). Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats. Molecular Medicine Reports, 16, 3233-3241. https://doi.org/10.3892/mmr.2017.6977
MLA
Wang, F., Wu, Z., Zha, X., Cai, Y., Wu, B., Jia, X., Zhu, D."Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats". Molecular Medicine Reports 16.3 (2017): 3233-3241.
Chicago
Wang, F., Wu, Z., Zha, X., Cai, Y., Wu, B., Jia, X., Zhu, D."Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats". Molecular Medicine Reports 16, no. 3 (2017): 3233-3241. https://doi.org/10.3892/mmr.2017.6977