Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats

Wang,Fen; Zeng,Xianzhong; Zhu,Yangbo; Ning,Dan; Liu,Junxia; Liu,Chunlei; Jia,Xuemei; Zhu,Defa

doi:10.3892/mmr.2014.2825

Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats

Authors:
- Fen Wang
- Xianzhong Zeng
- Yangbo Zhu
- Dan Ning
- Junxia Liu
- Chunlei Liu
- Xuemei Jia
- Defa Zhu
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Affiliations: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Comprehensive Laboratory, College of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: October 30, 2014 https://doi.org/10.3892/mmr.2014.2825
Pages: 775-782
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

A growing number of studies have revealed that neurocognitive impairment, induced by adult-onset hypothyroidism, may not be fully restored by traditional hormone substitution therapies, including thyroxine (T4). The present study has investigated the effect of T4 and donepezil (DON; an acetylcholinesterase (AChE) inhibitor) treatment on the hypothyroidism-induced alterations of acetylcholine (ACh) content and AChE activity. Furthermore, we examined synaptotagmin-1 (syt-1) and SNAP-25 expression in the hippocampus of adult rats. Adding 0.05% propylthiouracil to their drinking water for five weeks induced hypothyroidism in the rat models. From the fourth week, the rats were treated with T4, DON or a combination of both. Concentration of ACh and the activity of AChE was determined colorimetrically. The results demonstrated that hypothyroidism induced a signiﬁcant decrease of Ach content and AChE activity (by 17 and 34%, respectively), which were restored to control values by T4 administration. DON treatment also restored Ach to the normal level. Protein levels of syt-1 and SNAP-25 were determined by immunohistochemistry. The results demonstrated that syt-1 was expressed at significantly lower levels in hypothyroid rats, while SNAP-25 levels were notably higher compared with the controls. Two-week treatment with T4 alone failed to normalize the expression levels of these two proteins, while co-administration of T4 and DON was able to induce this effect. These data suggested that the thyroid hormone, T4, may have a direct effect on the metabolism of hippocampal ACh in adult rats, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism.

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