Developmental Hypothyroxinemia and Hypothyroidism Reduce Proliferation of Cerebellar Granule Neuron Precursors in Rat Offspring by Downregulation of the Sonic Hedgehog Signaling Pathway

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• 作者：Yuan Wang (1)
  Yi Wang (1)
  Jing Dong (1)
  Wei Wei (1)
  Binbin Song (1)
  Hui Min (1)
  Ye Yu (1)
  Xibing Lei (1)
  Ming Zhao (1)
  Weiping Teng (2)
  Jie Chen (1)
  
• 关键词：Iodine deficiency ; Hypothyroxinemia ; Hypothyroidism ; Cerebellar granule neuron precursors ; Proliferation ; Shh signaling pathway
• 刊名：Molecular Neurobiology
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：49
• 期：3
• 页码：1143-1152
• 全文大小：
• 参考文献：1. Puig-Domingo M, Vila L (2013) The implications of iodine and its supplementation during pregnancy in fetal brain development. Curr Clin Pharmacol 8:97鈥?09 CrossRef
  2. Zimmermann MB (2009) Iodine deficiency. Endocr Rev 30:376鈥?08 CrossRef
  3. Skeaff SA (2011) Iodine deficiency in pregnancy: the effect on neurodevelopment in the child. Nutrients 3:265鈥?73 CrossRef
  4. Berbel P, Obregon MJ, Bernal J, Escobar del Rey F, Morreale de Escobar G (2007) Iodine supplementation during pregnancy: a public health challenge. Trends Endocrinol Metab 18:338鈥?43 CrossRef
  5. Glinoer D (2001) Potential consequences of maternal hypothyroidism on the offspring: evidence and implications. Horm Res 55:109鈥?14 CrossRef
  6. Tang Z, Liu W, Yin H, Wang P, Dong J, Wang Y, Chen J (2007) Investigation of intelligence quotient and psychomotor development in schoolchildren in areas with different degrees of iodine deficiency. Asia Pac J Clin Nutr 16:731鈥?37
  7. Lavado-Autric R, Aus贸 E, Garc铆a-Velasco JV, Arufe Mdel C, Escobar del Rey F, Berbel P, Morreale de Escobar G (2003) Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J Clin Invest 111:1073鈥?082 CrossRef
  8. Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, Vulsma T, Wiersinga WM, Drexhage HA, Vader HL (1999) Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf) 50:149鈥?55 CrossRef
  9. Morreale de Escobar G, Obregon MJ, Escobar del Rey F (2004) Role of thyroid hormone during early brain development. Eur J Endocrinol 151:U25鈥揢37 CrossRef
  10. Morreale de Escobar G, Obregon MJ, Escobar del Rey F (2000) Is neuropsychological development related to maternal hypothyroidism or to maternal hypothyroxinemia? J Clin Endocrinol Metab 85:3975鈥?987
  11. Brooks VB (1984) Cerebellar functions in motor control. Hum Neurobiol 2:251鈥?60
  12. Hibi M, Shimizu T (2012) Development of the cerebellum and cerebellar neural circuits. Dev Neurobiol 72(3):282鈥?01 CrossRef
  13. Sillitoe RV, Joyner AL (2007) Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu Rev Cell Dev Biol 23:549鈥?77 CrossRef
  14. Vaillant C, Monard D (2009) SHH pathway and cerebellar development. Cerebellum 8(3):291鈥?01 CrossRef
  15. Behesti H, Marino S (2009) Cerebellar granule cells: insights into proliferation, differentiation, and role in medulloblastoma pathogenesis. Int J Biochem Cell Biol 41(3):435鈥?45 CrossRef
  16. Kumar K, Patro N, Patro I (2013) Impaired structural and functional development of cerebellum following gestational exposure of delta methrin in rats: role of reelin. Cell Mol Neurobiol 33(5):731鈥?46 CrossRef
  17. Kenney AM, Cole MD, Rowitch DH (2003) N-Myc upregulation by sonic hedgehog signaling promotes proliferation in developing cerebellar granule neuron precursors. Development 130(1):15鈥?8 CrossRef
  18. Dahmane N, Ruizi Altaba A (1999) Sonic hedgehog regulates the growth and patterning of the cerebellum. Development 126(14):3089鈥?100
  19. Manto MU, Jissendi P (2012) Cerebellum: links between development, developmental disorders and motor learning. Front Neuroanat 6:1
  20. Corrales JD, Rocco GL, Blaess S, Guo Q, Joyner AL (2004) Spatial pattern of sonic hedgehog signaling through Gli genes during cerebellum development. Development 131(22):5581鈥?590 CrossRef
  21. Oliver TG, Grasfeder LL, Carroll AL, Kaiser C, Gillingham CL, Lin SM, Wickramasinghe R, Scott MP, Wechsler-Reya RJ (2003) Transcriptional profiling of the sonic hedgehog response: a critical role for N-myc in proliferation of neuronal precursors. Proc Natl Acad Sci U S A 100(12):7331鈥?336 CrossRef
  22. Yun JS, Rust JM, Ishimaru T, D铆az E (2007) A novel role of the Mad family member Mad3 in cerebellar granule neuron precursor proliferation. Mol Cell Biol 27(23):8178鈥?189 CrossRef
  23. Kimura-Kuroda J, Nagata I, Negishi-Kato M, Kuroda Y (2002) Thyroid hormone-dependent development of mouse cerebellar Purkinje cells in vitro. Brain Res Dev Brain Res 137:55鈥?5 CrossRef
  24. Koibuchi N, Chin WW (2000) Thyroid hormone action and brain development. Trends Endocrinol Metab 11:123鈥?28 CrossRef
  25. Portella AC, Carvalho F, Faustino L, Wondisford FE, Ortiga-Carvalho TM, Gomes FC (2010) Thyroid hormone receptor beta mutation causes severe impairment of cerebellar development. Mol Cell Neurosci 44(1):68鈥?7 CrossRef
  26. Wang Y, Wei W, Wang Y, Dong J, Song B, Min H, Teng W, Chen J (2013) Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway. Toxicol Appl Pharmacol 271(2):257鈥?65 CrossRef
  27. Reeves PG, Nielsen FH, Fahey GC Jr (1993) AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 123:1939鈥?951
  28. Mills J, Niewmierzycka A, Oloumi A, Rico B, St-Arnaud R, Mackenzie IR, Mawji NM, Wilson J, Reichardt LF, Dedhar S (2006) Critical role of integrin-linked kinase in granule cell precursor proliferation and cerebellar development. J Neurosci 26(3):830鈥?40 CrossRef
  29. Argenti B, Gallo R, Di Marcotullio L, Ferretti E, Napolitano M, Canterini S, De Smaele E, Greco A, Fiorenza MT, Maroder M, Screpanti I, Alesse E, Gulino A (2005) Hedgehog antagonist REN(KCTD11) regulates proliferation and apoptosis of developing granule cell progenitors. J Neurosci 25(36):8338鈥?346 CrossRef
  30. Kenney AM, Widlund HR, Rowitch DH (2004) Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Development 131(1):217鈥?28 CrossRef
  31. Kawamori A, Shimaji K, Yamaguchi M (2013) Control of e2f1 and PCNA by / Drosophila transcription factor DREF. Genesis. doi: 10.1002/dvg.22419
  32. Vermiglio F, Lo Presti VP, Moleti M, Sidoti M, Tortorella G, Scaffidi G, Castagna MG, Mattina F, Violi MA, Cris脿 A, Artemisia A, Trimarchi F (2004) Attention deficit and hyperactivity disorders in the offspring of mothers exposed to mild鈥搈oderate iodine deficiency: a possible novel iodine deficiency disorder in developed countries. J Clin Endocrinol Metab 89:6054鈥?060 CrossRef
  33. Pedraza PE, Obregon MJ, Escobar-Morreale HF, del Rey FE, de Escobar GM (2006) Mechanisms of adaptation to iodine deficiency in rats: thyroid status is tissue specific. Its relevance for man. Endocrinology 147:2098鈥?108 CrossRef
  34. Dunn JT (1995) Thyroglobulin, hormone synthesis and thyroid disease. Eur J Endocrinol 132:603鈥?04 CrossRef
  35. Dunn JT, Dunn AD (2001) Update on intrathyroidal iodine metabolism. Thyroid 11:407鈥?14 CrossRef
  36. Isaia F, Aragoni MC, Arca M, Demartin F, Devillanova FA, Floris G, Garau A, Hursthouse MB, Lippolis V, Medda R, Oppo F, Pira M, Verani G (2008) Interaction of methimazole with I2: X-ray crystal structure of the charge transfer complex methimazole-I2 implications for the mechanism of action of methimazole-based antithyroid drugs. J Med Chem 51:4050鈥?053 CrossRef
  37. Shin MS, Ko IG, Kim SE, Kim BK, Kim TS, Lee SH, Hwang DS, Kim CJ, Park JK, Lim BV (2013) Treadmill exercise ameliorates symptoms of methimazole-induced hypothyroidism through enhancing neurogenesis and suppressing apoptosis in the hippocampus of rat pups. Int J Dev Neurosci 31:214鈥?23 CrossRef
  38. Manzano J, Cuadrado M, Morte B, Bernal J (2007) Influence of thyroid hormone and thyroid hormone recptors in the generation of cerebellar gamma-aminobutyric acid-ergic interneurons from precursor cells. Endocrinology 148(12):5746鈥?751 CrossRef
  39. Chantoux F, Francon J (2002) Thyroid hormone regulates the expression of NeuroD/BHF1 during the development of rat cerebellum. Mol Cell Endocrinol 194(1鈥?):157鈥?63 CrossRef
  40. Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, Vijlder JJ (2003) Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3 year follow-up study. Clin Endocrinol 59:282鈥?88 CrossRef
  41. Axelstad M, Hansen PR, Boberg J, Bonnichsen M, Nellemann C, Lund SP, Hougaard KS, Hass U (2008) Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes. Toxicol Appl Pharmacol 232(1):1鈥?3
  42. Farwell AP, Dubord-Tomasetti SA, Pietrzykowski AZ, Stachelek SJ, Leonard JL (2005) Regulation of cerebellar neuronal migration and neurite outgrowth by thyroxine and 3,3鈥?5鈥?triiodothyronine. Brain Res Dev Brain Res 154(1):121鈥?35 CrossRef
  43. Galliano E, Gao Z, Schonewille M, Todorov B, Simons E, Pop AS, D鈥橝ngelo E, van den Maagdenberg AM, Hoebeek FE, De Zeeuw CI (2013) Silencing the majority of cerebellar granule cells uncovers their essential role in motor learning and consolidation. Plant Cell Rep 3(4):1239鈥?251 CrossRef
  44. Jiao J, Nakajima A, Janssen WG, Bindokas VP, Xiong X, Morrison JH, Brorson JR, Tang YP (2008) Expression of NR2B in cerebellar granule cells specifically facilitates effect of motor training on motor learning. PLoS One 3(2):e1684 CrossRef
  45. Kim JC, Cook MN, Carey MR, Shen C, Regehr WG, Dymecki SM (2009) Linking genetically defined neurons to behavior through a broadly applicable silencing allele. Neuron 63(3):305鈥?15 CrossRef
  46. Seja P, Schonewille M, Spitzmaul G, Badura A, Klein I, Rudhard Y, Wisden W, H眉bner CA, De Zeeuw CI, Jentsch TJ (2012) Raising cytosolic Cl- in cerebellar granule cells affects their excitability and vestibule-ocular learning. EMBO J 31(5):1217鈥?230 CrossRef
  47. Desouza LA, Sathanoori M, Kapoor R, Rajadhyaksha N, Gonzalez LE, Kottmann AH, Tole S, Vaidya VA (2011) Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult mammalian brain. Endocrinology 152(5):1989鈥?000 CrossRef
  48. Knoepfler PS, Cheng PF, Eisenman RN (2002) N-myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation. Genes Dev 16:2699鈥?712 CrossRef
  49. Kenney AM, Rowitch DH (2000) Sonic hedgehog promotes G (1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors. Mol Cell Biol 20:9055鈥?067 CrossRef
  50. Pogoriler J, Millen K, Utset M, Du W (2006) Loss of cyclin D1 impairs cerebellar development and suppresses medulloblastoma formation. Development 133:3929鈥?937 CrossRef
  51. Huard JM, Forster CC, Carter ML, Sicinski P, Ross ME (1999) Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126:1927鈥?935
  52. Ciemerych MA, Kenney AM, Sicinska E, Kalaszczynska I, Bronson RT, Rowitch DH, Gardner H, Sicinski P (2002) Development of mice expressing a single D-type cyclin. Genes Dev 16:3277鈥?289 CrossRef
  53. Yang Y, Sun F, Zhang C, Wang H, Wu G, Wu Z (2013) Hypoxia promotes cell proliferation by modulating E2F1 in chicken pulmonary arterial smooth muscle cells. J Anim Sci Biotechnol 4(1):28 CrossRef
  54. Swarnalatha M, Singh AK, Kumar V (2013) Promoter occupancy of MLL1 histone methyltransferase seems to specify the proliferative and apoptotic functions of E2F1 in a tumour microenvironment. J Cell Sci 126: 4636鈥?646
  55. Bhatia B, Hsieh M, Kenney AM, Nahl茅 Z (2011) Mitogenic sonic hedgehog signaling drives E2F1-dependent lipogenesis in progenitor cells and medulloblastoma. Oncogene 30(4):410鈥?22 CrossRef
  
• 作者单位：Yuan Wang (1)
  Yi Wang (1)
  Jing Dong (1)
  Wei Wei (1)
  Binbin Song (1)
  Hui Min (1)
  Ye Yu (1)
  Xibing Lei (1)
  Ming Zhao (1)
  Weiping Teng (2)
  Jie Chen (1)
  
  1. Department of Occupational and Environmental Health, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang, 110001, People鈥檚 Republic of China
  2. Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, People鈥檚 Republic of China
  
• ISSN：1559-1182

文摘

Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during development result in dysfunction of the central nervous system, affecting psychomotor and motor function, although the underlying mechanisms causing these alterations are still unclear. Therefore, our aim is to study the effects of developmental hypothyroxinemia, caused by mild ID, and developmental hypothyroidism, caused by severe ID or methimazole (MMZ), on the proliferation of cerebellar granule neuron precursors (CGNPs), an excellent experimental model of cerebellar development and function. The sonic hedgehog (Shh) signaling pathway is essential for CGNP proliferation, and as such, its activation is also investigated here. A maternal hypothyroxinemia model was established in Wistar rats by administrating a mild ID diet, and two maternal hypothyroidism models were developed either by administrating a severe ID diet or MMZ water. Our results showed that hypothyroxinemia and hypothyroidism reduced proliferation of CGNPs on postnatal day (PN) 7, PN14, and PN21. Accordingly, the mean intensity of proliferating cell nuclear antigen and Ki67 nuclear antigen immunofluorescence was reduced in the mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of the Shh signaling pathway on PN7, PN14, and PN21. Our study supports the hypothesis that developmental hypothyroxinemia induced by mild ID, and hypothyroidism induced by severe ID or MMZ, reduce the proliferation of CGNPs, which may be ascribed to the downregulation of the Shh signaling pathway.