Wang Yuan, Dong Jing, Wang Yi, Wei Wei, Song Binbin, Shan Zhongyan, Teng Weiping, Chen Jie
Department of Occupational and Environmental Health, School of Public Health, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Biol Trace Elem Res. 2016 Oct;173(2):465-74. doi: 10.1007/s12011-016-0664-9. Epub 2016 Mar 31.
Iodine is a significant micronutrient. Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during developmental period can cause cerebellar dysfunction. However, mechanisms are still unclear. Therefore, the present research aims to study effects of developmental hypothyroxinemia caused by mild ID and hypothyroidism caused by severe ID or methimazole (MMZ) on parallel fiber-Purkinje cell (PF-PC) synapses in filial cerebellum. Maternal hypothyroxinemia and hypothyroidism models were established in Wistar rats using ID diet and deionized water supplemented with different concentrations of potassium iodide or MMZ water. Birth weight and cerebellum weight were measured. We also examined PF-PC synapses using immunofluorescence, and western blot analysis was conducted to investigate the activity of Neurexin1/cerebellin1 (Cbln1)/glutamate receptor d2 (GluD2) tripartite complex. Our results showed that hypothyroxinemia and hypothyroidism decreased birth weight and cerebellum weight and reduced the PF-PC synapses on postnatal day (PN) 14 and PN21. Accordingly, the mean intensity of vesicular glutamate transporter (VGluT1) and Calbindin immunofluorescence was reduced in mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of Neurexin1/Cbln1/GluD2 tripartite complex. Our study supports the hypothesis that developmental hypothyroxinemia and hypothyroidism reduce PF-PC synapses, which may be attributed to the downregulation of Neurexin1/Cbln1/GluD2 tripartite complex.
碘是一种重要的微量营养素。发育期碘缺乏（ID）所致的低甲状腺素血症和甲状腺功能减退可导致小脑功能障碍。然而，其机制仍不清楚。因此，本研究旨在探讨轻度ID所致发育性低甲状腺素血症以及重度ID或甲巯咪唑（MMZ）所致甲状腺功能减退对子代小脑平行纤维-浦肯野细胞（PF-PC）突触的影响。采用含ID饲料和补充不同浓度碘化钾的去离子水或MMZ水，在Wistar大鼠中建立母体低甲状腺素血症和甲状腺功能减退模型。测量出生体重和小脑重量。我们还使用免疫荧光检查PF-PC突触，并进行蛋白质免疫印迹分析以研究神经连接蛋白1/小脑素1（Cbln1）/谷氨酸受体d2（GluD2）三联体复合物的活性。我们的结果表明，低甲状腺素血症和甲状腺功能减退降低了出生体重和小脑重量，并减少了出生后第14天（PN）和PN21天的PF-PC突触。相应地，轻度ID、重度ID和MMZ组中囊泡谷氨酸转运体（VGluT1）和钙结合蛋白免疫荧光的平均强度降低。此外，母体低甲状腺素血症和甲状腺功能减退降低了神经连接蛋白1/Cbln1/GluD2三联体复合物的表达。我们的研究支持这样的假设，即发育性低甲状腺素血症和甲状腺功能减退会减少PF-PC突触，这可能归因于神经连接蛋白1/Cbln1/GluD2三联体复合物的下调。
