Department of Endocrinology, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Neurochem Res. 2019 Aug;44(8):1999-2006. doi: 10.1007/s11064-019-02836-y. Epub 2019 Jul 19.
Adult-onset hypothyroidism induces cognitive impairments in learning and memory. Thyroxin (T4) replacement therapy appears to be effective in biochemically restoring euthyroidism, as evidenced by serum T4 and triiodothyronine concentrations within the normal range, although some the patients still exhibit cognitive dysfunctions. Here, we investigated the cognitive functions of propylthiouracil-induced hypothyroid mice in C57BL/6j and 129/Sv strains using the passive avoidance task and the novel object recognition test. Cognitive dysfunctions in hypothyroid mice were found only in the C57BL/6j strain, not in the 129/Sv strain. Further, we found that cholinergic neurons in the basal forebrain increased the membrane potential and input resistance with decreased capacitance, and that they decreased the amplitude and width of action potential in hypothyroid mice in the C57BL/6j strain but not in those in the 129/Sv strain, compared with the controls for each strain. Additionally, the excitability of cholinergic neurons in the basal forebrain was reduced in the hypothyroid mice in the C57BL/6j strain. These results indicated that transgenic mice with the C57BL/6j genetic background are more suitable for revealing the mechanism underlying hypothyroidism-induced cognitive dysfunction, and that the cholinergic basal forebrain may be the appropriate target for treating cognitive dysfunction in adult-onset hypothyroidism.
成年期甲状腺功能减退症可导致学习和记忆认知障碍。甲状腺素（T4）替代疗法似乎可通过将血清 T4 和三碘甲状腺原氨酸浓度恢复至正常范围内，在生化上有效恢复甲状腺功能正常，尽管一些患者仍表现出认知功能障碍。在这里，我们使用被动回避任务和新物体识别测试，研究了丙基硫氧嘧啶诱导的 C57BL/6j 和 129/Sv 品系甲状腺功能减退症小鼠的认知功能。仅在 C57BL/6j 品系的甲状腺功能减退症小鼠中发现认知功能障碍，而在 129/Sv 品系的甲状腺功能减退症小鼠中未发现认知功能障碍。此外，我们发现，与每个品系的对照相比，在 C57BL/6j 品系的甲状腺功能减退症小鼠中，基底前脑的胆碱能神经元增加了膜电位和输入电阻，降低了电容，并且降低了动作电位的幅度和宽度。此外，在 C57BL/6j 品系的甲状腺功能减退症小鼠中，基底前脑胆碱能神经元的兴奋性降低。这些结果表明，具有 C57BL/6j 遗传背景的转基因小鼠更适合揭示甲状腺功能减退症引起的认知功能障碍的机制，并且胆碱能基底前脑可能是治疗成年期甲状腺功能减退症认知功能障碍的合适靶点。
