Department of Nuclear Medicine, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou 563000, China.
Department of Hospital Infection Management, The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, Guizhou 563000, China.
Aging (Albany NY). 2023 Mar 7;15(5):1591-1602. doi: 10.18632/aging.204570.
Studies showed that thyroid function plays an important role in the pathology of Alzheimer's disease (AD). However, changes in brain thyroid hormone and related receptors in the early stage of AD were rarely reported. The aim of this study was to explore the relationship between the early stage of AD and local thyroid hormone and its receptors in the brain.
The animal model was established by stereotactic injection of okadaic acid (OA) into hippocampal region for the experiment, and 0.9% NS for the control. Blood sample from each mouse was collected and then the mice were sacrificed and the brain tissue was collected for detecting free triiodothyronine (FT3), free thyroid hormone (FT4), and thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH) and phosphorylated tau, amyloid-β (Aβ) and thyroid hormone receptors (THRs) in the hippocampus of the mice were detected as well.
Enzyme-linked immunosorbent assay showed that compared with the control, FT3, FT4, TSH and TRH in brain were significantly increased in the experimental group; in the serum, FT4, TSH and TRH were increased, while FT3 had no change; western blot analysis indicated that the expression of THR α and β in the hippocampus of the experimental group was significantly higher than that of the control.
Based on the results of this study, a mouse AD model can be established successfully by injecting a small dose of OA into the hippocampus. We speculate that early AD brain and circulating thyroid dysfunction may be an early local and systemic stress repair response.
研究表明甲状腺功能在阿尔茨海默病（AD）的病理中起着重要作用。然而，AD 早期大脑中甲状腺激素及其相关受体的变化很少有报道。本研究旨在探讨 AD 早期与大脑局部甲状腺激素及其受体的关系。
采用立体定向注射 OKADAIC ACID（OA）制作海马区实验动物模型，以 0.9% NS 为对照。采集每组小鼠血样，处死小鼠取脑，检测各组小鼠海马组织游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、促甲状腺激素释放激素（TRH），并检测磷酸化 tau、淀粉样β（Aβ）及甲状腺激素受体（THRs）。
酶联免疫吸附试验显示，与对照组相比，实验组脑内 FT3、FT4、TSH 和 TRH 明显增加；血清中 FT4、TSH 和 TRH 增加，FT3 无变化；Western blot 分析表明，实验组海马 THRα和β表达明显高于对照组。
本研究结果成功建立了小剂量 OA 海马注射的 AD 小鼠模型，我们推测 AD 早期大脑和循环甲状腺功能障碍可能是早期局部和全身应激修复反应。
