title: Effects of thyroxine and donepezil on hippocampal acetylcholine content, acetylcholinesterase activity, synaptotagmin-1 and SNAP-25 expression in hypothyroid adult rats.
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.
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Yangbo
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ning
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Liu
authors.affiliation: Comprehensive Laboratory, College of Basic Medicine, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Defa
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000109:Acetylcholine / Q000032:analysis / Q000378:metabolism; D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000077265:Donepezil; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007037:Hypothyroidism / Q000188:drug therapy / Q000473:pathology*; D007150:Immunohistochemistry; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008163:Luminescent Measurements; D008297:Male; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000494:pharmacology* / Q000627:therapeutic use; D014284:Triiodothyronine / Q000097:blood
chemical_list: D013956:Antithyroid Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D050825:Synaptosomal-Associated Protein 25; D050863:Synaptotagmin I; D014284:Triiodothyronine; D011441:Propylthiouracil; D000077265:Donepezil; D013972:Thyrotropin; D000110:Acetylcholinesterase; D000109:Acetylcholine; D013974:Thyroxine