妊娠期轻度碘营养不足及早期补碘对子代大鼠小脑运动性学习记忆的影响及机制研究

Mild iodine deficiency during pregnancy and lactation is widespread. However, the effects of mild iodine deficiency on cerebellar motor learning are not reported, and the mechanisms remain unclear. It is controversial that iodine supplement in the first trimester of pregnancy can recover the damage of cerebellar motor learning induced by mild iodine deficiency. Previous studies have successfully obtained the animal model of mild iodine deficiency, found that mild iodine deficiency during pregnancy and lactation can inhibit cerebellar purkinje cells dendritic growth, reduce granule cells proliferation and differentiation, and damage cerebellum functional development. On this basis, we build rat model of iodine supplement during pregnancy by iodine deficiency diet and drank iodine deionized water to further study the effects of mild iodine deficiency and iodine supplement on synaptic plasticity and motor learning in offspring cerebella. The regulating effect of cerebellar purkinje cells LTD and AMPA associated factors will be analysed. The underlying mechanisms of cerebellar synaptic plasticity and motor learning in offspring by mild iodine deficiency and iodine supplement are clarified. Results of this study may contribute to formulate appropriate iodine related policies and prevent iodine nutritional deficiency during pregnancy and lactation women in our country.

轻度碘营养不足在妊娠期和哺乳期妇女人群中普遍存在，但其对小脑运动性学习记忆损伤的研究未见报道，机制尚不清楚。并且妊娠早期补碘能否恢复轻度碘营养不足对小脑运动性学习记忆的影响还存在争议。前期研究已成功获得轻度碘营养不足动物模型，发现妊娠期和哺乳期轻度碘营养不足可抑制小脑浦肯野细胞树突生长发育，损害颗粒细胞增殖和分化，造成小脑功能发育受损。在此基础上，我们通过控制大鼠每日低碘饲料和碘饮水的摄入量来建立妊娠期补碘动物模型，进一步研究轻度碘营养不足以及补碘后对仔鼠小脑突触可塑性和运动性学习记忆形成的影响，深入分析调控浦肯野细胞LTD及其AMPA受体相关因子的变化对仔鼠小脑运动功能的调节作用，具体阐明轻度碘营养不足以及补碘后影响小脑突触可塑性和运动性学习记忆形成的机制。为我国制定适宜补碘相关政策，对预防妊娠期和哺乳期妇女碘营养不足，提供科学依据。

轻度碘营养不足在妊娠期和哺乳期妇女人群中普遍存在，但其对小脑发育及运动协调性损伤的研究极少，机制尚不清楚。并且妊娠早期补碘能否恢复轻度碘营养不足对小脑发育及运动协调性的影响还存在争议。本研究通过控制大鼠每日低碘饲料和含不同浓度碘饮水的摄入量，成功建立了孕期及哺乳期轻度碘营养不足及早期补碘动物模型，并通过前肢握力、平衡木和旋转杆实验及测定相关蛋白来检测轻度碘营养不足及补碘对小脑运动协调性的影响，采用Golgi-Cox染色、免疫荧光及透射电镜等方法观察小脑浦肯野细胞的发育。研究发现妊娠期和哺乳期轻度碘营养不足损伤仔鼠小脑浦肯野细胞树突发育及超微结构，并通过抑制mGluR1信号途径而影响小脑运动协调性。妊娠早期补碘可改善由于轻度碘营养不足所造成的小脑浦肯野细胞受损及运动协调性障碍。这可能是其影响小脑运动性学习记忆的原因之一。此外，我们还发现轻度和重度碘营养不足可通过调控Shh信号通路抑制海马齿状回区神经前体细胞的表达和增殖。本研究为进一步认识和预防妊娠及哺乳期碘营养供应不足的危害，促进儿童智力发育、 提高人口素质，提供了实验基础。