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

Wang F, Zeng X, Zhu Y, Ning D, Liu J, Liu C, Jia X, Zhu D - Mol Med Rep (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

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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Concentration of hippocampal ACh from Hypo, T4, DON, T4+DON and C groups (n=10–12). Homogenates were extracted from the hippocampus of each rat. Hypothyroidism induced a significant decrease in ACh content in the hippocampus, and the DON (0.005%), T4 (6 μg/100 g body weight) or combined treatment (T4+DON) restored the Ach levels to the control value. Data shown are the mean ± SEM of three independent experiments. C, control group; Hypo, hypothyroid group; DON, hypothyroid rats treated with 0.005% (w/v) DON; T4, hypothyroid rats treated with 6 μg T4/100 g BW; T4+DON, hypothyroid rats treated with 6 μg T4/100 g BW beside adding 0.005% (w/v) DON to the drinking water. *P<0.05, vs C. ACh, acetylcholine; T4, thyroxine; DON, donepezil; Prot, hippocampus protein; SEM, standard error of the mean; w/v, weight/volume.
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f1-mmr-11-02-0775: Concentration of hippocampal ACh from Hypo, T4, DON, T4+DON and C groups (n=10–12). Homogenates were extracted from the hippocampus of each rat. Hypothyroidism induced a significant decrease in ACh content in the hippocampus, and the DON (0.005%), T4 (6 μg/100 g body weight) or combined treatment (T4+DON) restored the Ach levels to the control value. Data shown are the mean ± SEM of three independent experiments. C, control group; Hypo, hypothyroid group; DON, hypothyroid rats treated with 0.005% (w/v) DON; T4, hypothyroid rats treated with 6 μg T4/100 g BW; T4+DON, hypothyroid rats treated with 6 μg T4/100 g BW beside adding 0.005% (w/v) DON to the drinking water. *P<0.05, vs C. ACh, acetylcholine; T4, thyroxine; DON, donepezil; Prot, hippocampus protein; SEM, standard error of the mean; w/v, weight/volume.

Mentions: Alkaline hydroxylamine colorimetry was performed to detect the content of Ach in the hippocampus of the rats among the groups. ACh content in the hippocampus is illustrated in Fig. 1. Our results demonstrated that the amount of ACh was significantly decreased by 27% in the hypothyroid rats (P=0.027) and the content was restored to control values (P=0.212, 0.860 and 0.255, respectively) by DON, T4 or T4+DON treatment.


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

Wang F, Zeng X, Zhu Y, Ning D, Liu J, Liu C, Jia X, Zhu D - Mol Med Rep (2014)

Concentration of hippocampal ACh from Hypo, T4, DON, T4+DON and C groups (n=10–12). Homogenates were extracted from the hippocampus of each rat. Hypothyroidism induced a significant decrease in ACh content in the hippocampus, and the DON (0.005%), T4 (6 μg/100 g body weight) or combined treatment (T4+DON) restored the Ach levels to the control value. Data shown are the mean ± SEM of three independent experiments. C, control group; Hypo, hypothyroid group; DON, hypothyroid rats treated with 0.005% (w/v) DON; T4, hypothyroid rats treated with 6 μg T4/100 g BW; T4+DON, hypothyroid rats treated with 6 μg T4/100 g BW beside adding 0.005% (w/v) DON to the drinking water. *P<0.05, vs C. ACh, acetylcholine; T4, thyroxine; DON, donepezil; Prot, hippocampus protein; SEM, standard error of the mean; w/v, weight/volume.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262484&req=5

f1-mmr-11-02-0775: Concentration of hippocampal ACh from Hypo, T4, DON, T4+DON and C groups (n=10–12). Homogenates were extracted from the hippocampus of each rat. Hypothyroidism induced a significant decrease in ACh content in the hippocampus, and the DON (0.005%), T4 (6 μg/100 g body weight) or combined treatment (T4+DON) restored the Ach levels to the control value. Data shown are the mean ± SEM of three independent experiments. C, control group; Hypo, hypothyroid group; DON, hypothyroid rats treated with 0.005% (w/v) DON; T4, hypothyroid rats treated with 6 μg T4/100 g BW; T4+DON, hypothyroid rats treated with 6 μg T4/100 g BW beside adding 0.005% (w/v) DON to the drinking water. *P<0.05, vs C. ACh, acetylcholine; T4, thyroxine; DON, donepezil; Prot, hippocampus protein; SEM, standard error of the mean; w/v, weight/volume.
Mentions: Alkaline hydroxylamine colorimetry was performed to detect the content of Ach in the hippocampus of the rats among the groups. ACh content in the hippocampus is illustrated in Fig. 1. Our results demonstrated that the amount of ACh was significantly decreased by 27% in the hypothyroid rats (P=0.027) and the content was restored to control values (P=0.212, 0.860 and 0.255, respectively) by DON, T4 or T4+DON treatment.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

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.

Show MeSH
Related in: MedlinePlus