scholarly journals Fetal and Neonatal Iron Deficiency Reduces Thyroid Hormone-Responsive Gene mRNA Levels in the Neonatal Rat Hippocampus and Cerebral Cortex

Endocrinology ◽  
2012 ◽  
Vol 153 (11) ◽  
pp. 5668-5680 ◽  
Author(s):  
Thomas W. Bastian ◽  
Jeremy A. Anderson ◽  
Stephanie J. Fretham ◽  
Joseph R. Prohaska ◽  
Michael K. Georgieff ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Neonatal Rat ◽  
Fe Deficiency ◽  
Common Mechanism ◽  
Mrna Levels ◽  
Micronutrient Deficiencies ◽  
Sprague Dawley ◽  
Whole Brain ◽  
Responsive Gene

Abstract Copper (Cu), iron (Fe), and thyroid hormone (TH) deficiencies produce similar defects in late brain development including hypomyelination of axons and impaired synapse formation and function, suggesting that these micronutrient deficiencies share a common mechanism contributing to these derangements. We previously demonstrated that fetal/neonatal Cu and Fe deficiencies lower circulating TH concentrations in neonatal rats. Fe deficiency also reduces whole-brain T3 content, suggesting impaired TH action in the developing Fe-deficient brain. We hypothesized that fetal/neonatal Cu and Fe deficiencies will produce mild or moderate TH deficiencies and will impair TH-responsive gene expression in the neonatal cerebral cortex and hippocampus. To test this hypothesis, we rendered pregnant Sprague Dawley rats Cu-, Fe-, or TH-deficient from early gestation through postnatal d 10 (P10). Mild and moderate TH deficiencies were induced by 1 and 3 ppm propylthiouracil treatment, respectively. Cu deficiency did not significantly alter serum or tissue TH concentrations or TH-responsive brain mRNA expression. Fe deficiency significantly lowered P10 serum total T3 (45%), serum total T4 (52%), whole brain T3 (14%), and hippocampal T3 (18%) concentrations, producing a mild TH deficiency similar to 1 ppm propylthiouracil treatment. Fe deficiency lowered Pvalb, Enpp6, and Mbp mRNA levels in the P10 hippocampus. Fe deficiency also altered Hairless, Dbm, and Dio2 mRNA levels in the P10 cerebral cortex. These results suggest that some of the brain defects associated with Fe deficiency may be mediated through altered thyroidal status and the concomitant alterations in TH-responsive gene transcription.

scholarly journals Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 4055-4065 ◽  
Author(s):  
Thomas W. Bastian ◽  
Joseph R. Prohaska ◽  
Michael K. Georgieff ◽  
Grant W. Anderson
Keyword(s):  
Thyroid Hormone ◽  
Brain Development ◽  
Neonatal Rat ◽  
Common Mechanism ◽  
Micronutrient Deficiencies ◽  
Whole Brain ◽  
Pregnant Rat ◽  
Cu Deficiency ◽  
Thyroidal Status ◽  
D 12

Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T4) and triiodothyronine (T3), and brain T3 levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T3 by 48%, serum total T4 by 21%, and whole-brain T3 by 10% at P12. Fe deficiency reduced serum total T3 by 43%, serum total T4 by 67%, and whole-brain T3 by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels.

Prenatal iodine deficiency results in structurally and functionally immature lungs in neonatal rats

2012 ◽  
Vol 302 (10) ◽  
pp. L1037-L1043 ◽  
Author(s):  
Madan M. Godbole ◽  
Geeta Rao ◽  
B. N. Paul ◽  
Vishwa Mohan ◽  
Preeti Singh ◽  
...  
Keyword(s):  
Drinking Water ◽  
Thyroid Hormone ◽  
Respiratory Distress ◽  
Lung Development ◽  
Thyroid Hormone Receptor ◽  
Alveolar Epithelium ◽  
Lung Compliance ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Deficient Diet

Maternal hypothyroidism affects postnatal lung structure. High prevalence of hypothyroxinemia (low T4, normal T3) in iodine-deficient pregnant women and associated risk for neuropsychological development along with high infant/neonatal mortality ascribed to respiratory distress prompted us to study the effects of maternal hypothyroxinemia on postnatal lung development. Female Sprague Dawley rats were given a low-iodine diet (LID) with 1% KClO4in drinking water for 10 days, to minimize thyroid hormone differences. Half of these rats were continued on iodine-deficient diet; ID (LID with 0.005% KClO4) for 3 mo, whereas the rest were switched to an iodine-sufficient diet; IS [LID + potassium iodide (10 μg iodine/20 g of diet + normal drinking water)]. Pups born to ID mothers were compared with age-matched pups from IS mothers at postnatal days 8 (P8) and 16 (P16) ( n = 6–8/group). ID pups had normal circulating T3 but significantly low T4 levels ( P < 0.05) and concomitantly approximately sixfold higher thyroid hormone receptor-β mRNA in alveolar epithelium. Lung histology revealed larger and irregularly shaped alveoli in ID pups relative to controls. Lung function was assessed at P16 using a double-chambered plethysmograph and observed reduced tidal volume, peak inspiratory and expiratory flow, and dynamic lung compliance in ID pups compared with IS pups. Significant lowering of surfactant protein (SP)-B and SP-C mRNA and protein found in ID pups at P16. ID pups had 16-fold lower matrix metalloproteinase-9 mRNA levels in their alveolar epithelium. In addition, mRNA levels of thyroid transcription factor-1 and SP-D were significantly higher (3-fold) compared with IS pups. At P16, significantly lower levels of SP-B and SP-C found in ID pups may be responsible for immature lung development and reduced lung compliance. Our data suggest that maternal hypothyroxinemia may result in the development of immature lungs that, through respiratory distress, could contribute to the observed high infant mortality in ID neonates.

scholarly journals Simple Method to Isolation and Culture of Neuron Progenitor Cells (NPCs) from Whole Brain Post-Natal Rat

2018 ◽  
Vol 9 (2) ◽  
pp. 63-69
Author(s):  
ARIYANI NOVIANTARI ◽  
Masagus Zainuri ◽  
Ratih Rinendyaputri ◽  
Ni Ketut Susilarini
Keyword(s):  
Progenitor Cells ◽  
Neuronal Cell ◽  
Neonatal Rat ◽  
Sprague Dawley ◽  
Simple Method ◽  
Whole Brain ◽  
Culture Cells ◽  
Result Show ◽  
Neuronal Cell Lines

Background: Using of neuron cells for in vitro neurobiology study is needed. Neuron cell can be obtained from a primary neuron or neuronal cell lines, depend on the aim of the study because both are not equivalent. Various methods are performed to obtain primary neurons from the cortical, hippocampal and whole brain of pre or neonatal rat. The limitations of neuron cells to proliferate so that is necessary to develop a method to isolate neuron progenitor cells (NPCs). The aim of the present study was to isolate NPCs from whole brain post-natal rat.   Methods: Whole brain were obtained from neonates Sprague Dawley rat. There are 2 step to get NSC; first isolation by taking the brain into the 15 ml of tube with 1 ml of  0,05% trypsin EDTA for 400g brain (incubated in the 370C, 5% CO2 for 10 minutes),  tirturation with adding 1 ml culture medium  and 5 ml HBSS-glucose then filtered by 70μm pore size membrane and centrifuged  2000 rpm for 10 minutes. Second: remove of supernatant with add 1 ml of HBSS-Glucose and taking it into a tube with  35% and 65% concentration of Ficoll then centrifuged at 1800 g for 10 minutes then supernatant were replated twice with poly D lysine (100µg/ml). Characterization of progenitor neuron immunotype was checked by immunohistochemistry with positive marker (NeuN and MAP2) and flow cytometry (PSANCAM+ and A2B5 -). Results: In this study, our result show that this method does not take longer than one hours and > 95% cells that obtained are expressing PSANCAM+.  After 4 days culture, cells exhibit positive for neuron marker as MAP2 and NeuN.   Conclusion: The method that our develope to isolate neuron progenitor cell from whole-brain are more effective and more simple with high viability and purity.

Negative regulation of the rat Na-K-ATPase alpha 3-subunit gene promoter by thyroid hormone

1996 ◽  
Vol 271 (5) ◽  
pp. C1750-C1756 ◽  
Author(s):  
H. He ◽  
S. Chin ◽  
K. Zhuang ◽  
R. Hartong ◽  
J. Apriletti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Cardiac Myocytes ◽  
Reporter Gene ◽  
Reporter Gene Expression ◽  
Neonatal Rat ◽  
Proximal Promoter ◽  
Mrna Levels ◽  
Neonatal Rat Cardiac Myocytes ◽  
Rat Cardiac Myocytes

Na-K-ATPase alpha 3-subunit mRNA levels are both positively and negatively controlled by thyroid hormone [3,5,3'triiodothyronine (T3)] in primary cultures of neonatal rat cardiac myocytes. In this study, transient transfection analysis indicated that two regions of the rat alpha 3 gene between nucleotides -116 and -6 and -6 and +80 conferred T3-mediated inhibition of reporter gene expression. Electrophoretic mobility shift assays showed specific binding of T3 receptor monomers and T3 receptor-retinoid X receptor heterodimers at each alpha 3 gene negative T3-response region. The alpha 3 gene region from -116 to -6 base pairs also mediates repression in response to retinoic acid (RA) and binds RA receptor. In the absence of ligand, reporter gene expression driven by the -116 to -6-base pair region is repressed with cotransfection of T3 receptor, whereas it is unaffected by overexpression of RA receptor. These data demonstrate that the proximal promoter of the rat Na-K-ATPase alpha 3 gene contains sequence motifs that mediate repression of alpha 3 gene transcription in response to either T3 or RA in neonatal rat cardiac myocytes.

Thyroid hormone-induced stimulation of the sarcoplasmic reticulum Ca2+ ATPase gene is inhibited by LIF and IL-6

2000 ◽  
Vol 278 (4) ◽  
pp. E738-E743 ◽  
Author(s):  
Bernd Gloss ◽  
Sonia Villegas ◽  
Francisco J. Villarreal ◽  
Anselmo Moriscot ◽  
Wolfgang H. Dillmann
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Myocytes ◽  
Transcriptional Activity ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Cytokine Inhibition ◽  
Atpase Gene ◽  
Promoter Construct

We investigated the effects of the leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) on 3,3′, 5-triiodo-l-thyronine, or thyroid hormone (T3)-stimulated sarcoplasmic reticulum Ca2+ATPase (SERCA2) gene expression on cultured neonatal rat cardiac myocytes. A reduction of T3 induced increases in SERCA2 mRNA levels after co-treatment with LIF or IL-6. To investigate for the molecular mechanism(s) responsible for the blunted gene expression, a 3.2-kb SERCA2 promoter construct containing a reporter gene was transfected into cardiac myocytes. T3 treatment stimulated transcriptional activity twofold, whereas co-treatment with T3 and either of the cytokines caused an inhibition of T3-induced SERCA2 transcriptional activity. A T3-responsive 0.6-kb SERCA2 construct also showed a similar inhibition by cytokines. Cytokine inhibition of SERCA2 transcriptional activity was also evident when a 0.6-kb SERCA2 mutant, T3-unresponsive promoter construct was used. Treatment with T3 and cytokines showed a significant decrease in transcription when a reporter construct was used that was comprised of direct repeats of SERCA2 thyroid response element I. These data provide evidence for cytokine-mediated inhibitory effects on the SERCA2 promoter that may be mediated by interfering with T3action.

scholarly journals Influence of hyperthyroid conditions on gene expression in extraocular muscles of rats

2009 ◽  
Vol 37 (3) ◽  
pp. 231-238 ◽  
Author(s):  
Thomas S. Postler ◽  
Murat T. Budak ◽  
Tejvir S. Khurana ◽  
Neal A. Rubinstein
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Protein Localization ◽  
Muscle Growth ◽  
Extraocular Muscles ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Wide Range ◽  
Canonical Pathways

Extraocular muscles (EOMs) are a highly specialized type of tissue with a wide range of unique properties, including characteristic innervation, development, and structural proteins. Even though EOMs are frequently and prominently affected by thyroid-associated diseases, little is known about the direct effects of thyroid hormone on these muscles. To create a comprehensive profile of changes in gene expression levels in EOMs induced by thyroid hormone, hyperthyroid conditions were simulated by treating adult Sprague-Dawley rats with intraperitoneal injections of the thyroid hormone 3,3′,5-triiodo-l-thyronine (T3); subsequently, microarray analysis was used to determine changes in mRNA levels in EOMs from T3-treated animals relative to untreated control animals. The expression of 468 transcripts was found to be significantly altered, with 466 of these transcripts downregulated in EOMs from T3-treated animals. The biological processes into which the affected genes could be grouped included cellular metabolism, transport, biosynthesis, protein localization, and cell homeostasis. Moreover, 15 distinct biochemical canonical pathways were represented among the genes with altered transcription levels. Strikingly, myostatin ( Gdf8), a potent negative regulator of muscle growth, was found to be strongly downregulated in EOMs from T3-treated animals. Together, these findings suggest that pathological concentrations of thyroid hormone have a unique effect on gene expression in EOMs, which is likely to play a hitherto neglected role in thyroid-associated ophthalmopathies.

Mechanical activity in heart regulates translation of α-myosin heavy chain mRNA but not its localization

1999 ◽  
Vol 276 (6) ◽  
pp. H2013-H2019 ◽  
Author(s):  
Gordana Nikcevic ◽  
Maria C. Heidkamp ◽  
Merja Perhonen ◽  
Brenda Russell
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Mrna Translation ◽  
Neonatal Rat ◽  
Mechanical Activity ◽  
Mrna Levels ◽  
Rat Cardiomyocytes ◽  
Significant Difference ◽  
Polysomal Fraction ◽  
Mechanical Transduction

Mechanical inactivity depresses protein expression in cardiac muscle tissue and results in atrophy. We explore the mechanical transduction mechanism in spontaneously beating neonatal rat cardiomyocytes expressing the α-myosin heavy chain (α-MyHC) isoform by interfering with cross-bridge function [2,3-butanedione monoxime (BDM), 7.5 mM] without affecting cell calcium. The polysome content and α-MyHC mRNA levels in fractions from a sucrose gradient were analyzed. BDM treatment blocked translation at initiation (162 ± 12% in the nonpolysomal RNA fraction and 43 ± 6% in the polysomal fraction, relative to control as 100%; P < 0.05). There was an increase in α-MyHC mRNA from the nonpolysomal fraction (120.5 ± 7.7%; P < 0.05 compared with control) with no significant change in the heavy polysomes. In situ hybridization of α-MyHC mRNA was used to estimate message abundance as a function of the distance from the nucleus. The mRNA was dispersed through the cytoplasm in spontaneously beating cells as well as in BDM-treated cells (no significant difference). We conclude that direct inhibition of contractile machinery, but not calcium, regulates initiation of α-MyHC mRNA translation. However, calcium, not pure mechanical signals, appears to be important for message localization.

scholarly journals Thyroid Hormone Action in Cerebellum and Cerebral Cortex Development

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Fabrice Chatonnet ◽  
Frédéric Picou ◽  
Teddy Fauquier ◽  
Frédéric Flamant
Keyword(s):  
Cerebral Cortex ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Glial Cell ◽  
Nuclear Receptors ◽  
Target Genes ◽  
Cell Types ◽  
Hormone Action ◽  
Cerebral Cortex Development ◽  
Thyroid Hormone Action

Thyroid hormones (TH, including the prohormone thyroxine (T4) and its active deiodinated derivative 3,,5-triiodo-L-thyronine (T3)) are important regulators of vertebrates neurodevelopment. Specific transporters and deiodinases are required to ensure T3 access to the developing brain. T3 activates a number of differentiation processes in neuronal and glial cell types by binding to nuclear receptors, acting directly on transcription. Only few T3 target genes are currently known. Deeper investigations are urgently needed, considering that some chemicals present in food are believed to interfere with T3 signaling with putative neurotoxic consequences.

scholarly journals Differential Effects of Refeeding on Melanocortin-Responsive Neurons in the Hypothalamic Paraventricular Nucleus

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4329-4335 ◽  
Author(s):  
Edith Sánchez ◽  
Praful S. Singru ◽  
Runa Acharya ◽  
Monica Bodria ◽  
Csaba Fekete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Early Action ◽  
Sprague Dawley Rats ◽  
Melanocortin Signaling ◽  
Agouti Related Protein ◽  
Serum Tsh

To explore the effect of refeeding on recovery of TRH gene expression in the hypothalamic paraventricular nucleus (PVN) and its correlation with the feeding-related neuropeptides in the arcuate nucleus (ARC), c-fos immunoreactivity (IR) in the PVN and ARC 2 h after refeeding and hypothalamic TRH, neuropeptide Y (NPY) and agouti-related protein (AGRP) mRNA levels 4, 12, and 24 h after refeeding were studied in Sprague-Dawley rats subjected to prolonged fasting. Despite rapid reactivation of proopiomelanocortin neurons by refeeding as demonstrated by c-fos IR in ARC α-MSH-IR neurons and ventral parvocellular subdivision PVN neurons, c-fos IR was present in only 9.7 ± 1.1% hypophysiotropic TRH neurons. Serum TSH levels remained suppressed 4 and 12 h after the start of refeeding, returning to fed levels after 24 h. Fasting reduced TRH mRNA compared with fed animals, and similar to TSH, remained suppressed at 4 and 12 h after refeeding, returning toward normal at 24 h. AGRP and NPY gene expression in the ARC were markedly elevated in fasting rats, AGRP mRNA returning to baseline levels 12 h after refeeding and NPY mRNA remaining persistently elevated even at 24 h. These data raise the possibility that refeeding-induced activation of melanocortin signaling exerts differential actions on its target neurons in the PVN, an early action directed at neurons that may be involved in satiety, and a later action on hypophysiotropic TRH neurons involved in energy expenditure, potentially mediated by sustained elevations in AGRP and NPY. This response may be an important homeostatic mechanism to allow replenishment of depleted energy stores associated with fasting.

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