Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
The Cerebellum
Published in: The Cerebellum 4/2008

01-12-2008

The Role of Thyroid Hormone on Cerebellar Development

Author: Noriyuki Koibuchi

Published in: The Cerebellum | Issue 4/2008

Login to get access

Abstract

Thyroid hormone plays a crucial role in cerebellar development. Deficiency of thyroid hormone results in abnormal cerebellar growth and differentiation. In rodent, thyroid hormone mainly affects cerebellar development during the first 2 weeks of postnatal life. Thyroid hormone replacement after such critical period cannot fully rescue abnormal cerebellar development induced by perinatal hypothyroidism. Thyroid hormone receptor (TR) is a ligand-regulated transcription factor that binds to a specific DNA sequence called thyroid-hormone-responsive element. TR recruits various coregulators such as coactivator and corepressor in a ligand-dependent manner to regulate transcription of target genes. In cerebellum, at least three different TRs are expressed in a cell-specific manner. TRβ1 is expressed predominantly in the Purkinje cell, whereas TRα1 in other subset of neurons. Although these TRs are widely expressed during the cerebellar development and their levels are greater in adult, the expression of many thyroid-hormone-responsive genes is altered by thyroid hormone status only during early postnatal critical period. Not only the expression levels of TRs but also those of cofactors and other nuclear receptors may play a role in regulating thyroid hormone sensitivity in the developing cerebellum. In this article, the effect of thyroid hormone on morphological development of cerebellum and molecular mechanisms of thyroid hormone action are introduced. Furthermore, possible involvement of other nuclear receptors and cofactors in thyroid hormone action in the developing cerebellum is also discussed.
Literature
1.
Koibuchi N, Chin WW (2000) Thyroid hormone action and brain development. Trends Endocrinol Metab 11:123–128PubMedCrossRef
2.
Koibuchi N, Jingu H, Iwasaki T, Chin WW (2003) Current perspectives on the role of thyroid hormone in growth and development of cerebellum. Cerebellum 2:279–289PubMedCrossRef
3.
Legrand J (1979) Morphogenetic actions of thyroid hormones. Trends Neurosci 2:234–236CrossRef
4.
Nicholson JL, Altman J (1972) The effects of early hypo- and hyperthyroidism on the development of the rat cerebellar cortex. II. Synaptogenesis in the molecular layer. Brain Res 44:25–36PubMedCrossRef
5.
Nicholson JL, Altman J (1972) Synaptogenesis in the rat cerebellum: effects of early hypo- and hyperthyroidism. Science 176:530–532PubMedCrossRef
6.
Nicholson JL, Altman J (1972) The effects of early hypo- and hyperthyroidism on development of rat cerebellar cortex. I. Cell proliferation and differentiation. Brain Res 44:13–23PubMedCrossRef
7.
Balázs R, Brooksbandk BWL, Patel AJ, Johnson AL, Wilson DA (1971) Incorporation of [35S] sulfate into brain constituents during development and the effects of thyroid hormone on myelination. Brain Res 30:273–293PubMedCrossRef
8.
Hajós F, Patel AJ, Balázs R (1973) Effect of thyroid deficiency on the synaptic organization of the rat cerebellar cortex. Brain Res 50:387–401PubMedCrossRef
9.
Bernal J (2005) The significance of thyroid hormone transporter in the brain. Endocrinology 146:1698–1700PubMedCrossRef
10.
Calvo R, Obregón MJ, Ruiz de Oña C, Escobar del Rey F, Morreale de Escobar G (1990) Congenital hypothyroidism, as studied in rats. J Clin Invest 86:889–899PubMedCrossRef
11.
Bradley DJ, Towle HC, Young WS (1992) Spatial and temporal expression of α- and β-thyroid hormone receptor mRNAs, including the β2-subtype, in the developing mammalian nervous system. J Neurosci 12:2288–2302PubMed
12.
Glass CK, Rosenfeld MG (2000) The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 14:121–141PubMed
13.
Koibuchi N, Yamaoka S, Chin WW (2001) Effects of altered thyroid status in neurotrophin gene expression during postnatal development of the mouse cerebellum. Thyroid 11:205–210PubMedCrossRef
14.
Misiti S, Koibuchi N, Bei M, Farsetti A, Chin WW (1999) Expression of steroid receptor coactivator-1 mRNA in the developing mouse embryo: a possible role in olfactory epithelium development. Endocrinology 140:1957–1960PubMedCrossRef
15.
Martinez de Arrieta C, Koibuchi N, Chin WW (2000) Coactivator and corepressor gene expression in rat cerebellum during postnatal development and the effect of altered thyroid status. Endocrinology 141:1693–1698PubMedCrossRef
16.
Yousefi B, Jingu H, Ohta M, Umezu M, Koibuchi N (2005) Postnatal changes of steroid receptor coactivator-1 immunoreactivity in rat cerebellar cortex. Thyroid 15:314–319PubMedCrossRef
17.
Nishihara E, Yoshida-Komiya H, Chan CS, Liao L, Davis RL, O'Malley BW, Xu J (2003) SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells. J Neurosci 23:213–222PubMed
18.
Messer A, Maskin P, Snodgrass GL (1984) Effects of triiodothyronine (T3) on the development of rat cerebellar cells in culture. Int J Dev Neurosci 2:277–285CrossRef
19.
Thompson CC, Bottcher M (1997) The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors. Proc Natl Acad Sci U S A 94:8527–8532PubMedCrossRef
20.
Iwasaki T, Koibuchi N, Chin WW (2005) Synovial sarcoma translocation (SYT) encodes a nuclear receptor coactivator. Endocrinology 146:3892–3899PubMedCrossRef
21.
Qiu C-H, Shimokawa N, Iwasaki T, Parhar IS, Koibuchi N (2007) Alteration of cerebellar neurotrophin messenger ribonucleic acids and the lack of thyroid hormone receptor augmentation by staggerer-type retinoic acid receptor-related orphan receptor-α mutation. Endocrinology 148:1745–1753PubMedCrossRef
22.
Koibuchi N, Chin WW (1998) RORα gene expression in the perinatal rat cerebellum: ontogeny and thyroid hormone regulation. Endocrinology 139:2335–2341PubMedCrossRef
23.
Koibuchi N, Liu Y, Fukuda H, Takeshita A, Yen PM, Chin WW (1999) RORα augments thyroid hormone receptor-mediated transcriptional activation. Endocrinology 140:1356–1364PubMedCrossRef
24.
Koibuchi N, Iwasaki T (2006) Regulation of brain development by thyroid hormone and its modulation by environmental chemicals. Endocrine J 53:295–303CrossRef
25.
Kimura-Kuroda J, Nagata I, Kuroda Y (2005) Hydroxylated metabolites of polychlorinated biphenyls inhibit thyroid-hormone-dependent extension of cerebellar Purkinje cell dendrites. Brain Res Dev Brain Res 154:259–263PubMedCrossRef
26.
Iwasaki T, Miyazaki W, Takeshita A, Kuroda Y, Koibuchi N (2002) Polychlorinated biphenyls suppress thyroid hormone-induced transactivation. Biochem Biophys Res Commun 299:384–388PubMedCrossRef
27.
Miyazaki W, Iwasaki T, Takeshita A, Kuroda Y, Koibuchi N (2004) Polychlorinated biphenyls suppress thyroid hormone receptor-mediated transcription through a novel mechanism. J Biol Chem 279:18195–18202PubMedCrossRef
28.
Miyazaki W, Iwasaki T, Takeshita A, Tohyama C, Koibuchi N (2008) Identification of functional domain of thyroid hormone receptor responsible for polychlorinated biphenyl-mediated suppression of its action in vitro. Environ Health Perspect 116:1231–1236PubMedCrossRef
29.
Göthe S, Wang Z, Ng L, Kindblom JM, Campos Barros A, Ohlsson C, Vennström B, Forrest D (1999) Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation. Gene Dev 13:1329–1341PubMedCrossRef
30.
Hashimoto K, Curty FH, Borges PP, Lee CE, Abel EDA, Elmquist JK, Cohen RN, Wondisford FE (2001) An unliganded thyroid hormone receptor causes severe neurological dysfunction. Proc Natl Acad Sci U S A 98:3998–4003PubMedCrossRef
31.
Morte B, Manzano J, Scanlan T, Vennström B, Bernal J (2001) Deletion of the thyroid hormone receptor α1 prevents the structural alterations of the cerebellum induced by hypothyroidism. Proc Natl Acad Sci U S A 99:3985–3989CrossRef
Metadata
Title
The Role of Thyroid Hormone on Cerebellar Development
Author
Noriyuki Koibuchi
Publication date
01-12-2008
Publisher
Springer-Verlag
Published in
The Cerebellum / Issue 4/2008
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-008-0069-1

Other articles of this Issue 4/2008

The Cerebellum 4/2008 Go to the issue

OriginalPaper

Cerebellar Disorders in Childhood: Cognitive Problems

OriginalPaper

Purkinje Cell Input to Cerebellar Nuclei in Tottering: Ultrastructure and Physiology

OriginalPaper

Development of Cerebellar GABAergic Interneurons: Origin and Shaping of the “Minibrain” Local Connections

OriginalPaper

Separate Neural Substrates in the Human Cerebellum for Sensory-motor Adaptation of Reactive and of Scanning Voluntary Saccades

OriginalPaper

Synaptic Integration in Cerebellar Granule Cells

OriginalPaper

Lesion-Symptom Mapping of the Human Cerebellum