Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning 110001, People's Republic of China; Liaoning Provincial Key Laboratory of Endocrine Diseases, China Medical University, Shenyang, People's Republic of China; Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, People's Republic of China.
Environ Toxicol. 2014 Aug;29(8):847-55. doi: 10.1002/tox.21811. Epub 2012 Sep 15.
We evaluated the role of p35 in the maturation of hippocampal granule neurons in offspring caused by developmental iodine deficiency. Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil-adulterated water (5 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day 28. The protein levels of p35, cyclin-dependent kinase 5, β-catenin, and N-cadherin were assessed on postnatal day 14, 21, and 28. Dendritic morphogenesis of newborn granule neurons in dentate gyrus was examined. Developmental hypothyroidism induced by iodine deficiency and PTU treatment delayed the maturation of hippocampal granule neurons in the offspring and decreased the percentage of Dcx-positive neurons that expressed β-catenin on postnatal day 21 and 28. In addition, downregulation of p35 was observed in dentate gyrus of hypothyroid groups. Developmental hypothyroidism induced by iodine deficiency and PTU treatment could delay the maturation of newborn granule neurons in dentate gyrus, and this deficit may be attributed to the downregulation of p35.
我们评估了 p35 在碘缺乏发育引起的后代海马颗粒神经元成熟中的作用。在妊娠第 6 天至出生后第 28 天，通过碘缺乏饮食或丙硫氧嘧啶污染水（5ppm）损害甲状腺功能，建立了两个发育大鼠模型。在出生后第 14、21 和 28 天评估了 p35、周期蛋白依赖性激酶 5、β-连环蛋白和 N-钙黏蛋白的蛋白水平。检查了新生颗粒神经元在齿状回的树突形态发生。碘缺乏和 PTU 处理引起的发育性甲状腺功能减退症延迟了后代海马颗粒神经元的成熟，并降低了在出生后第 21 和 28 天表达β-连环蛋白的 Dcx 阳性神经元的百分比。此外，在甲状腺功能减退组的齿状回中观察到 p35 的下调。碘缺乏和 PTU 处理引起的发育性甲状腺功能减退症可延迟新生颗粒神经元在齿状回中的成熟，这种缺陷可能归因于 p35 的下调。
