title: Developmental Hypothyroxinemia and Hypothyroidism Reduce Parallel Fiber-Purkinje Cell Synapses in Rat Offspring by Downregulation of Neurexin1/Cbln1/GluD2 Tripartite Complex.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Binbin
authors.initials: B
authors.lastname: Song
authors.affiliation: Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Teng
authors.affiliation: 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. chenjie@mail.cmu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015536:Down-Regulation; D005260:Female; D005969:Glutamate Dehydrogenase / Q000096:biosynthesis*; D007037:Hypothyroidism / Q000378:metabolism* / Q000473:pathology; D007455:Iodine / Q000172:deficiency*; D046912:Multiprotein Complexes / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011498:Protein Precursors / Q000096:biosynthesis*; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
chemical_list: C538940:Cbln1 protein, rat; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C547193:Nrxn1 protein, rat; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D007455:Iodine; D005969:Glutamate Dehydrogenase
keywords: Cerebellum; Hypothyroidism; Hypothyroxinemia; Iodine deficiency; Neurexin1/Cbln1/GluD2 tripartite complex; Parallel fiber–Purkinje cell synapses