Abstract
Among the most dramatic actions of thyroid hormone are those exerted on brain development and function. In the adult human brain, a deficiency or excess of thyroid hormone may lead to various psychiatric manifestations, but it is during development when thyroid hormone exerts its most varied and critical actions on neural tissue. In humans, a deficiency of thyroid hormone taking place during a critical period of development may lead to severe mental retardation and also to neurological defects (1). This critical period may extend from the start of the second trimester of pregnancy to the first few months after birth. During this period, the absence of thyroid hormone, if not corrected by early postnatal treatment, leads to irreversible damage with mental retardation. While in utero, the fetal brain is protected from thyroid deficiency by the maternal hormone. Severe thyroid hormone deficiency in the pregnant woman, especially if combined with fetal deficiency, leads to severe neurological deficits in the child that are irreversible even with early postnatal treatment.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Porterfield, S. P. and Hendrich, C. E. (1993) The role of thyroid hormones in prenatal and neonatal neurological development-current perspectives. Endocr. Rev. 14, 94–106.
Legrand, J. (1984) Effects of thyroid hormones on central nervous system, in Neurobehavioral Teratology (Yanai, J., ed.), Elsevier Science Publishers, Amsterdam, pp. 331–363.
Pérez-Castillo, A., Bernal, J., Ferreiro, B., and Pans, T. (1985) The early ontogenesis of thyroid hormone receptor in the rat fetus. Endocrinology 117, 2457–2461.
Bradley, D. J., Towle, H. C., and Young, W. S. (1992) Spatial and temporal expression of α-and β-thyroid hormone receptor mRNAs, including the β2-sub-type, in the developing mammalian nervous system. J. Neurosci. 12, 2288–2302.
Bernal, J. and Pekonen, F. (1984) Ontogenesis of the nuclear 3,5,3′-triiodothyro-nine receptor in the human fetal brain. Endocrinology 114, 677–679.
Bernal, J. and Guadaño-Ferraz, A. (1998) Thyroid hormone and the development of the brain. Curr. Op. Endocrinol. Diabetes 5, 296–302.
Rogister, B., Ben-Hur, T., and Dubois-Dalcq, M. (1999) From neural stem cells to myelinating oligodendrocytes. Mol. Cell. Neurosci. 14, 287–300.
Sutcliffe, J. G. (1988) The genes for myelin revisited. Trends Genet. 4, 211–213.
Vega-Núñez, E., Menéndez-Hurtado, A., Garesse, R., Santos, A., and PerezCastillo, A. (1995) Thyroid hormone-regulated brain mitochondrial genes revealed by differential cDNA cloning. J. Clin. Invest. 96, 893–899.
Alvarez-Dolado, M., Gonzalez-Moreno, M., Valencia, A., Zenke, M., Bernal, J., and Muñoz, A. (1999a) Identification of a mammalian homologue of the fungal Tom70 mitochondrial precursor protein import receptor as a thyroid hormone-regulated gene in specific brain regions. J. Neurochem. 73, 2240–2249.
Iglesias, T., CaubÍn, J., Zaballos, A., Bernal, J., and Muñoz, A. (1995) Identification of the mitochondrial NADH dehydrogenase subunit 3 (ND3) as a thyroid hormone regulated gene by whole genome PCR analysis. Biochem. Biophys. Res. Comm. 210, 995–1000.
Alvarez-Dolado, M., Iglesias, T., RodrÍguez-Peña, A., Bernal, J., and Muñoz, A. (1994) Expression of neurotrophins and the trk family of neurotrophin receptors in normal and hypothyroid rat brain. Mol. Brain Res. 27, 249–257.
Neveu, I. and Arenas, E. (1996) Neurotrophins promote the survival and development of neurons in the cerebellum of hypothyroid rats. J. Cell Biol. 133, 631–646.
Aniello, F., Couchie, D., Gripois, D., and Nunez, J. (1991) Regulation of five tubulin isotypes by thyroid hormone during brain development. J. Neurochem. 57, 1781–1786.
Aniello, F., Couchie, D., Bridoux, A. M., Gripois, D., and Nunez, J. (1991) Splicing of juvenile and adult tau mRNA variants is regulated by thyroid hormone. Proc. Natl. Acad. Sci. USA 88, 4035–039.
Ghorbel, M. T., Seugnet, I., Hadj-Sahraoui, N., Topilko, P., Levi, G., and Demeneix, B. (1999) Thyroid hormone effects on Krox-24 transcription in the post-natal mouse brain are developmentally regulated but are not correlated with mitosis. Oncogene 18, 917–924.
Koibuchi, N. and Chin, W. W. (1998) RORα gene expression in the perinatal rat cerebellum: ontogeny and thyroid hormone regulation. Endocrinology 139, 2335–2341.
Denver, R. J., Ouellet, L., Furling, D., Kobayashi, A., Fujii-Kuriyama, Y., and Puymirat, J. (1999) Basic transcription element-binding protein (BTEB) is a thyroid hormone-regulated gene in the developing central nervous system. Evidence for a role in neurite outgrowth. J. Biol. Chem. 274, 23,128–23,134.
Cuadrado, A., Bernal, J., and Muñoz, A. (1999) Identification of the mammalian homolog of the splicing regulator Suppressor-of-white-apricot as a thyroid hormone regulated gene. Mol. Brain. Res. 71, 332–340.
Alvarez-Dolado, M., Gonzalez-Sancho, J. M., Bernal, J., and Muñoz, A. (1998) Developmental expression of tenascin-C is altered by hypothyroidism in the rat brain. Neuroscience 84, 309–322.
Alvarez-Dolado, M., Ruiz, M., del Rio, J. A., et al. (1999b) Thyroid hormone regulates reelin and dab1 expression during brain development. J. Neurosci. 19, 6979–6973.
Alvarez-Dolado, M., Cuadrado, A., Navarro-Yubero, C., et al. (2000) Regulation of the L1 cell adhesion molecule by thyroid hormone in the developing brain. Mol. Cell. Neurobiol. 16, 499–514.
Iñiguez, M. A., De Lecea, L., Guadaño-Ferraz, A., et al. (1996) Cell-specific effects of thyroid hormone on RC3/neurogranin expression in rat brain. Endocrinology 137, 1032–1041.
Krebs, J. and Honegger, P. (1996) Calmodulin kinase IV: expression and function during rat brain development. Biochim. Biophys. Acta 1313, 217–222.
GarcÍa-Fernández, L. F., Urade, Y., Hayaishi, O., Bernal, J., and Muñoz, A. (1998) Identification of a thyroid hormone response element in the promoter region of the rat lipocalin-type prostaglandin D synthase (beta-trace) gene. Mol. Brain Res. 55, 321–330.
Falk, J. D., Vargiu, P., Foye, P. E., et al. (1999) Rhes: a striatal-specific Ras homolog related to Dexras1. J. Neurosci. Res. 57, 782–788.
Valentino, K. L., Eberwine, J. H., and Barchas, J. D. (1987) In Situ Hybridization: Applications to Neurobiology, Oxford University Press, New York.
Wisden, W. and Morris, B. J. (1994) In Situ Hybridization Protocols for the Brain, Academic Press, London.
Polak, J. M. and McGee, J. O. D. (1998) In Situ Hybridization: Principles and Practice, Oxford University Press, Oxford.
Obregón, M. J., Ruiz de Oña, C., Calvo, R., Escobar del Rey, F., and Morreale de Escobar, G. (1991) Outer ring iodothyronine deiodinases and thyroid hormone economy: responses to iodine deficiency in the rat fetus and neonate. Endocrinology 129, 2663–2673.
Guadaño-Ferraz, A., Escámez, M. J., Morte, B., Vargiu, P., and Bernal, J. (1997) Transcriptional induction of RC3/neurogranin by thyroid hormone: differential neuronal sensitivity is not correlated with thyroid hormone receptor distribution in the brain. Mol. Brain Res. 49, 37–4.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Humana Press Inc.
About this protocol
Cite this protocol
Bernal, J., Guadaño-Ferraz, A. (2002). Analysis of Thyroid Hormone-Dependent Genes in the Brain by In Situ Hybridization. In: Baniahmad, A. (eds) Thyroid Hormone Receptors. Methods in Molecular Biology, vol 202. Humana Press. https://doi.org/10.1385/1-59259-174-4:71
Download citation
DOI: https://doi.org/10.1385/1-59259-174-4:71
Publisher Name: Humana Press
Print ISBN: 978-0-89603-995-7
Online ISBN: 978-1-59259-174-9
eBook Packages: Springer Protocols