Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, PR China.
BMC Neurosci. 2009 Dec 18;10:149. doi: 10.1186/1471-2202-10-149.
Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.
Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42.
The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42.
Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.
发育性碘缺乏会导致甲状腺激素不足，从而损害学习和记忆，但其机制尚不清楚。在这里，我们表明，在发育期碘缺乏和甲状腺功能减退症后，哺乳期和青春期大鼠海马中海马细胞外信号调节激酶（ERK1/2）和 cAMP 反应元件结合蛋白（CREB）的细胞外信号调节激酶（ERK1/2）和 cAMP 反应元件结合蛋白（CREB）参与了学习和记忆的损害。
通过给予孕鼠碘缺乏饮食或丙基硫氧嘧啶（PTU，5ppm 或 15ppm）添加饮用水，从妊娠第 6 天（GD）到产后第 28 天（PN），建立了 3 种发育性大鼠模型。然后，在 PN14、PN21、PN28 和 PN42 时，用 Western blot 检测海马中的总和磷酸化 ERK1/2 以及总和磷酸化 CREB。
碘缺乏和甲状腺功能减退的幼鼠血清 FT3 和 FT4 水平较低，体重较小，睁眼延迟。与对照组相比，碘缺乏和 15ppmPTU 处理组的海马中存活细胞的平均数量明显减少（P <0.05）。碘缺乏和 15ppmPTU 处理组的总和磷酸化 ERK1/2 和 CREB 水平明显低于对照组（P <0.05）。在 PN42 时，甲状腺激素浓度的恢复并不能使 ERK1/2 和 CREB 的减少逆转。
发育期碘缺乏和甲状腺功能减退症可下调哺乳期和青春期大鼠海马中的 ERK1/2 和 CREB。
