Department of Physiology, Medical Faculty, Gaziosmanpasa University, Tokat, Turkey.
Department of Pathology, Medical Faculty, Erciyes University, Kayseri, Turkey.
Int J Neurosci. 2022 Jul;132(7):662-672. doi: 10.1080/00207454.2020.1835898. Epub 2020 Nov 10.
We investigated protective effect of sodium selenite (Se) on hypothyroidism-induced impairments in, Morris water maze (MWM), long-term potentiation (LTP) and hippocampal neurogenesis male Wistar rats aged of 2 months.
Hypothyroidism was induced by administration of propylthiouracil (Ptu, 1 mg/kg/d) solution to the rats from postnatal day 60 for 81 days with or without Se (0.5mg/kg/d). Neurogenesis was examined by Ki-67 immunohistochemical staining. Se values on plasma and hippocampus were measured with inductively coupled plasma-mass spectrometry (ICP-MS).
Measurement of fT3 and fT4 levels confirmed that the fT3 levels, but not fT4, in Ptu-treated rats (5435.44±816.05 fg/ml, < 0.05) has returned to control values (8721.66±2567.68 fg/ml) by Se treatment (8661.65±711.43 fg/ml). Analysis of learning performance in water escape learning task showed that Se supplementation disappeared memory deficit in Ptu-treated rats as shown by significantly decreased time spent in the target quadrant (33.7±0.24% in control group; 26.1±0.48% in Ptu-group, < 0.05; 33.9±0.44 in Ptu+Se group), although there was no significant difference among groups in any measurement of learning performance on the last day. Considering LTP, Se supplementation improved the deficit in synaptic plasticity in Ptu-treated rats, as shown by significant increase in the excitatory postsynaptic potential slope (% 243±31 in control group; 172±49 in Ptu-group, < 0.05; 222±65 in Ptu+Se group) without affecting of the impairment in somatic plasticity. Se supplementation did not improve the decrease in the number of progenitor cells in the subgranular layer (SGL) of dentate gyrus (DG) of Ptu treated rats.
These findings suggest that selenium supplementation in hypothyroid patients may improve learning and memory disorders with different physiological mechanisms.HighlightsSe increased serum fT3 levels and hippocampus Se levels in hypothyroid rats.Se attenuated impairment of population spike-LTP in hypothyroid ratsHypothyroidism disrupts neurogenesis process in the dentate gyrus of hippocampus.Se supplementation could not increase new born cells in hypothyroid rats.
我们研究亚硒酸钠（Se）对甲状腺功能减退症诱导的雄性 Wistar 大鼠空间学习和记忆障碍、长时程增强（LTP）和海马神经发生的保护作用。
从出生后第 60 天开始，每天给大鼠腹腔注射丙硫氧嘧啶（Ptu，1mg/kg/d）溶液，连续 81 天，诱导甲状腺功能减退症。用 Ki-67 免疫组化染色法检测神经发生。用电感耦合等离子体质谱法（ICP-MS）测量血浆和海马中的 Se 值。
测量游离三碘甲状腺原氨酸（fT3）和游离甲状腺素（fT4）水平证实，Ptu 处理组大鼠（5435.44±816.05fg/ml，<0.05）的 fT3 水平，但不是 fT4 水平，通过 Se 处理（8661.65±711.43fg/ml）恢复到对照值（8721.66±2567.68fg/ml）。在水迷宫逃避学习任务中的学习表现分析表明，Se 补充剂消除了 Ptu 处理组大鼠的记忆缺陷，表现为在目标象限中花费的时间明显减少（对照组为 33.7±0.24%；Ptu 组为 26.1±0.48%，<0.05；Ptu+Se 组为 33.9±0.44%），尽管在最后一天的任何学习表现测量中，各组之间没有显著差异。考虑到 LTP，Se 补充剂改善了 Ptu 处理组大鼠突触可塑性的缺陷，表现为兴奋性突触后电位斜率显著增加（对照组为 243±31%；Ptu 组为 172±49%，<0.05；Ptu+Se 组为 222±65%），而不影响体细胞可塑性的损伤。Se 补充剂并没有改善 Ptu 处理大鼠齿状回颗粒下层（DG）祖细胞数量的减少。
这些发现表明，在甲状腺功能减退症患者中补充硒可能会通过不同的生理机制改善学习和记忆障碍。
Se 增加了甲状腺功能减退症大鼠的血清 fT3 水平和海马 Se 水平。
Se 减轻了甲状腺功能减退症大鼠群体峰-LTP 的损伤。
甲状腺功能减退症破坏了海马齿状回的神经发生过程。
Se 补充剂不能增加甲状腺功能减退症大鼠的新生细胞。
