title: Perinatal iodine deficiency and hypothyroidism increase cell apoptosis and alter doublecortin and reelin protein expressions in rat cerebellum.
abstract: OBJECTIVE
  Adequate thyroid hormone is critical for cerebellar development. Developmental hypothyroidism induced by iodine deficiency during the perinatal period results in permanent impairments of cerebellar development with an unclear mechanism. In the present study we investigated effects of perinatal iodine deficiency and hypothyroidism on cerebellar cell apoptosis, doublecortin (Dcx) and reelin. Apoptosis is an essential part of neural development. Dcx and reelin are two important molecules involved in neuronal migration, structure, and development in cerebellum.
  
  
  METHODS
  Two developmental rat models were created by administering dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 until postnatal day (PND) 28. TUNEL assay and protein levels of Dcx and reelin in cerebella were assessed on PND14, 21 and 28.
  
  
  RESULTS
  Apoptotic cells were increased in the iodine-deficient and PTU-treated rats. Dcx protein levels in the cerebella of iodine-deficient and PTU-treated rats were significantly downregulated on PND14. Interestingly, iodine deficiency and PTU treatment upregulated the levels of Dcx protein on PND21 and 28. Reelin expressions in iodine-deficient and PTU-treated rats were significantly decreased on PND14 and 21. On PND28, reelin expressions of three treated groups were still lower than control group, although without significant difference.
  
  
  CONCLUSIONS
  These findings may implicate alterations in cell apoptosis and levels of Dcx and reelin in the impairments of cerebellar development induced by developmental iodine deficiency and hypothyroidism.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jiapeng
authors.initials: J
authors.lastname: Zhong
authors.forename: Hongde
authors.initials: H
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Gong
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.forename: Weiping
authors.initials: W
authors.lastname: Teng
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D002531:Cerebellum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007037:Hypothyroidism / Q000139:chemically induced / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007455:Iodine / Q000172:deficiency*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011441:Propylthiouracil / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D013963:Thyroid Hormones / Q000097:blood / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; C000717129:Reln protein, rat; D013963:Thyroid Hormones; D011441:Propylthiouracil; D007455:Iodine; D012697:Serine Endopeptidases