School of Pharmacy, Anhui Medical University, Hefei, China.
J Neuroendocrinol. 2012 Jun;24(6):953-61. doi: 10.1111/j.1365-2826.2012.02297.x.
It is well known that clinical hypothyroidism (CH) can induce cognitive deficits, and the decision to start treatment for CH with thyroxine is usually straightforward. However, the relationship of cognition dysfunction with subclinical hypothyroidism (SCH) is inconsistent, and the decision concerning the need to treat SCH is controversial. In the present study, we induced a SCH rat model by hemi-thyroid electrocauterisation; then employed a serial of behavioural tests, including a beam balance, open field task and Morris water maze (MWM), to investigate the behaviour performance of SCH rats; and finally explored the protein expression of phosphorylated extracellular signal-regulated kinase (ERK)1/2 in the hippocampus by western blotting. The results demonstrated that hemi-thyroid electrocauterised rats had an elevated plasma thyrotrophin-stimulating hormone (TSH) level, with normal free thyroxine (fT4) and triiodothyronine (T3) concentrations, which defines SCH in humans. If rat SCH is diagnosed according to measurements of both plasma TSH higher than 97.5 percentile for the sham group and fT4 in the range 2.5-97.5 percentile for the sham group, the success rate of SCH modelling was 66.6%. SCH decreased exploratory behaviour but did not affect motor function in rats, showing a negative correlation of exploratory behaviour with plasma TSH concentration. Moreover, SCH rats displayed an impairment of learning and memory ability in the MWM task, with a longer escape latency in the acquisition phase and a shorter duration in the target quadrant in the test phase compared to that of sham rats. The mechanism for this might be related to the increased plasma TSH concentration, the decreased hippocampal T3 level and the enhanced expression of phosphorylated ERK1/2 in the hippocampus. The results of the present study, together with the results obtained in other studies, suggest that treatment is necessary for SCH.
众所周知，临床甲状腺功能减退症（CH）可引起认知功能障碍，而开始使用甲状腺素治疗 CH 的决定通常是明确的。然而，亚临床甲状腺功能减退症（SCH）与认知功能障碍的关系并不一致，治疗 SCH 的必要性存在争议。在本研究中，我们通过半甲状腺电灼术诱导 SCH 大鼠模型；然后采用一系列行为测试，包括平衡木、旷场实验和 Morris 水迷宫（MWM），来研究 SCH 大鼠的行为表现；最后通过 Western blot 法检测海马磷酸化细胞外信号调节激酶（ERK）1/2 的蛋白表达。结果表明，半甲状腺电灼大鼠的血浆促甲状腺素刺激激素（TSH）水平升高，游离甲状腺素（fT4）和三碘甲状腺原氨酸（T3）浓度正常，这定义了人类的 SCH。如果根据血浆 TSH 高于 sham 组 97.5 百分位数且 fT4 处于 sham 组 2.5-97.5 百分位数来诊断大鼠 SCH，则 SCH 模型的成功率为 66.6%。SCH 降低了大鼠的探索行为，但不影响其运动功能，探索行为与血浆 TSH 浓度呈负相关。此外，SCH 大鼠在 MWM 任务中表现出学习和记忆能力受损，在获得阶段的逃避潜伏期较长，在测试阶段的目标象限持续时间较短。这种机制可能与血浆 TSH 浓度升高、海马 T3 水平降低以及海马磷酸化 ERK1/2 表达增强有关。本研究结果与其他研究结果表明，SCH 需要治疗。
