Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, and Behavioral Studies

Stein, Stuart A.; Adams, Perrie M.; Shanklin, Douglas R.; Mihailoff, Gregory A.; Palnitkar, Maya

doi:10.1007/978-1-4684-5973-9_4

Cited by 47 publications

(42 citation statements)

References 80 publications

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“…Spatial learning and memory is severely impaired on the radial arm maze (5) and Morris water maze (6), as well as on other complex mazes (40). Congenitally hypothyroid children have cognitive deficits not unlike those observed in neonatally hypothyroid rats.…”

Section: Role Of Hormones In Brain Development and Cognitionmentioning

confidence: 95%

“…Neonatal hypothyroidism results in delayed myelinogenesis, alterations in cell migration, delayed or impaired neuronal differentiation and synaptogenesis, and alterations in neurotransmitter function (2)(3)(4). These morphologic and neurochemical changes are associated with permanent impairments in neurobehavioral function, including delayed reflex development, changes in motor activity and emotionality, and deficits in learning and memory (5,6,40). Although thyroid hormone imbalances during adulthood can also lead to cognitive and behavioral disturbances, these are usually completely reversible with appropriate hormone therapy.…”

Section: Role Of Hormones In Brain Development and Cognitionmentioning

confidence: 99%

“…Disruption of the thyroid system during development has been shown to result in permanent changes in neurochemical (2), morphologic (3,4), and neurobehavioral end points (5)(6)(7). There are a number of environmental contaminants that have been shown to affect thyroid system function (8).…”

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confidence: 99%

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Cognitive effects of endocrine-disrupting chemicals in animals.

Schantz

Widholm

2001

Environ Health Perspect

221

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A large number of chemical pollutants including phthalates, alkylphenolic compounds, polychlorinated biphenyls and polychlorinated dibenzodioxins, organochlorine pesticides, bisphenol A, and metals including lead, mercury, and cadmium have the ability to disrupt endocrine function in animals. Some of these same chemicals have been shown to alter cognitive function in animals and humans. Because hormonally mediated events play a central role in central nervous system development and function, a number of researchers have speculated that the changes in cognitive function are mediated by the endocrine-like actions of these chemicals. In this paper we review the evidence that cognitive effects of chemicals classified as environmental endocrine disruptors are mediated by changes in hormonal function. We begin by briefly reviewing the role of gonadal steroids, thyroid hormones, and glucocorticoids in brain development and brain function. We then review the endocrine changes and cognitive effects that have been reported for selected endocrine-disrupting chemicals, discuss the evidence for causal relationships between endocrine disruption and cognitive effects, and suggest directions for future research.

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Section: Role Of Hormones In Brain Development and Cognitionmentioning

confidence: 95%

Section: Role Of Hormones In Brain Development and Cognitionmentioning

confidence: 99%

See 1 more Smart Citation

Cognitive effects of endocrine-disrupting chemicals in animals.

Schantz

Widholm

2001

Environ Health Perspect

221

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“…Any impairment in the supply of THs to the developing nervous system leads to severe and irreversible abnormalities of brain structure and function, causing mental retardation in humans (161)(162)(163)(164)(165)(166). A particularly TH-sensitive stage of brain development is one at which post-mitotic neurons undertake the outgrowth of axonal and dendritic processes and start establishing and stabilizing the synaptic contacts, while oligodendroglial cells are actively engaged in myelin synthesis.…”

Section: Thyroid Hormone Effects On the Nervous Systemmentioning

confidence: 99%

Thyroid hormones and the central nervous system of mammals (Review)

Liegro

2008

Mol Med Report

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Abstract. The thyroid hormones (THs) L-thyroxine (T4) and L-triiodothyronine (T3) have a profound influence on the development and maturation of the mammalian brain, both before and after birth. Any impairment in the supply of THs to the developing nervous system leads to severe and irreversible changes in both the overall architecture and functions of the brain and causes, in humans, neurological and motor deficits known as cretinism. Pronounced neurological symptoms are also commonly observed in adult patients suffering from both hyperthyroidism and hypothyroidism, and it has recently emerged that certain symptoms might result from the reduced brain uptake, rather than the insufficient production, of THs. Most of the effects of THs are mediated by two classes of nuclear receptors (α and ß isoforms), which belong to the c-erbA superfamily of transcriptional regulators and are expressed in a tissue-specific and developmentally regulated manner. Interestingly, the nuclear TH receptors (nTRs) act as both ligand-independent gene repressors and ligand-dependent gene activators. On the other hand, negatively-regulated genes, which can be stimulated in the absence of THs and repressed by THs, have also been observed. Due to this complex pattern of regulation, the effects of receptor dysfunction do not exactly overlap the effects of hormone deficiency or excess. Moreover, non-genomic mechanisms of TH action have been described in many tissues, including the brain, some of which seem to be mediated by integrins and to be calcium-dependent. Intracellular receptors, distinct from nTRs, are present in the mitochondria, where a matrix-associated, T3-dependent transcriptional regulator of approximately 43 kDa has been described. Finally, complex patterns of pituitary and/or peripheral resistance to thyroid hormones (RTH), characterized by elevated plasma levels of THs and non-suppressible thyroidstimulating hormone (TSH), have been identified. This review summarizes the major advances in knowledge of the molecular mechanisms of TH action and their implication for the effects of THs on the developing, as well as the adult mammalian, nervous system.

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“…Also, T4 inhibits the activity of deiodinase 2 (D2) at the post-translational level including the microfilaments (Actin) [50]. The window of time for TH-dependent regulation of these processes is limited to pre-and perinatal life in rodents [42][43][44][45] neuronal cytoskeleton and neuronal growth either by affecting the developmental programs for expression of specific isoforms [50][51][52][53][54][55][56][57][58][59]. Thus, I may infer that thyroid disorders during the development can disrupt the cytoskeleton system, mitochondrial functions and gene expression.…”

mentioning

confidence: 99%

Perinatal Hypothyroidism and Cytoskeleton Dysfunction

Rg¹

2017

Endocrinol Metab Syndr

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Thyroid hormones (THs) are necessary for normal development particularly cytoskeletal system. Cytoskeletal system which consists of microtubules (Tubulin), microfilaments (Actin), and intermediate filaments, specific for neurons (Neurofilaments), glia (Glial Fibrillary Acidic Protein), or maturing cells (Vimentin, Nestin) can play important roles in neural cell shape and neuronal migration and outgrowth . THs regulate and reorganize this system by nongenomic actions. Moreover, THs regulate the expression of extracellular matrix (ECM) and adhesion molecules that are important for neuronal migration and development, such as tenascin-C, neural cell adhesion molecule (N-CAM), reelin and dab1, laminin and fibronectin. Maternal THs controls the expression of neuronal migration and growth, branching of neurites, astrocytic cytoskeletal proteins, cell cycle regulators, neurotrophins and neurotrophin receptors and extracellular matrix proteins in the fetal brain [41][42][43][44][45].In maternal hypothyroidism, there was reduction in the expression of GFAP protein in fetal brain in late gestation. In neonatal hypothyroid rats, the actin fibers are disorganized in brain (cerebellum). Also, the disruptions of laminin and developing cerebellum of hypothyroid rats were observed by Farwell et al. [40][41][42][43][44][45]. This alters the development of cellular cytoskeleton, synthesis of microtubule protein, axonal transport, neuronal outgrowth and neuronal behavior. These abnormalities might be attributed to the abnormalities in the development of cellular cytoskeleton (stabilization and composition of microtubule protein and in the delivery of cytoskeletal proteins to developing terminals via the slow component of axonal transport [40][41][42][43][44][45][46][47][48]. In parallel, the early postnatal hypothyroidism in rats raises both RNA and protein levels of tenascin-C in cerebellar Bergmann glia. On the other hand, Evans et al. [40] reported that maternal hyperthyroidism changes the expression of neuronal cytoskeletal proteins and accelerate the fetal neuronal differentiation. In agreement with this result, hypothyroidism reduced the matrix glia protein (MGP) mRNA levels while hyperthyroidism upregulated the MGP gene [34]. Moreover, the neurotrophins, in particular brain-derived neurotrophic factor (BDNF), are important in the course of development and are reduced in hypothyroidism [48][49][50] and increased in hyperthyroidism [30]. Also, T4 inhibits the activity of deiodinase 2 (D2) at the post-translational level including the microfilaments (Actin) [50]. The window of time for TH-dependent regulation of these processes is limited to pre-and perinatal life in rodents [42][43][44][45] neuronal cytoskeleton and neuronal growth either by affecting the developmental programs for expression of specific isoforms [50][51][52][53][54][55][56][57][58][59]. Thus, I may infer that thyroid disorders during the development can disrupt the cytoskeleton system, mitochondrial functions and gene expression. Further work is therefore r...

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Thyroid Hormone Control of Brain and Motor Development: Molecular, Neuroanatomical, and Behavioral Studies

Cited by 47 publications

References 80 publications

Cognitive effects of endocrine-disrupting chemicals in animals.

Cognitive effects of endocrine-disrupting chemicals in animals.

Thyroid hormones and the central nervous system of mammals (Review)

Perinatal Hypothyroidism and Cytoskeleton Dysfunction

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