scholarly journals Thyroid Hormone Insufficiency during Brain Development Reduces Parvalbumin Immunoreactivity and Inhibitory Function in the Hippocampus

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 92-102 ◽  
Author(s):  
M. E. Gilbert ◽  
L. Sui ◽  
M. J. Walker ◽  
W. Anderson ◽  
S. Thomas ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Dentate Gyrus ◽  
Perforant Path ◽  
High Dose ◽  
Synaptic Inhibition ◽  
Inhibitory Function ◽  
Inhibitory Circuitry ◽  
Dose Dependent

Thyroid hormones are necessary for brain development. γ-Amino-butyric acid (GABA)ergic interneurons comprise the bulk of local inhibitory circuitry in brain, many of which contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe postnatal hypothyroidism reduces PV immunoreactivity (IR) in rat neocortex. We examined PV-IR and GABA-mediated synaptic inhibition in the hippocampus of rats deprived of thyroid hormone from gestational d 6 until weaning on postnatal d 30. Pregnant dams were exposed to propylthiouracil (0, 3, 10 ppm) via the drinking water, which decreased maternal serum T4 by approximately 50–75% and increased TSH. At weaning, T4 was reduced by approximately 70% in offspring in the low-dose group and fell below detectable levels in high-dose animals. PV-IR was diminished in the hippocampus and neocortex of offspring killed on postnatal d 21, an effect that could be reversed by postnatal administration of T4. Dose-dependent decreases in the density of PV-IR neurons were observed in neocortex and hippocampus, with the dentate gyrus showing the most severe reductions (50–75% below control counts). Altered staining persisted to adulthood despite the return of thyroid hormones to control levels. Developmental cross-fostering and adult-onset deprivation studies revealed that early postnatal hormone insufficiency was required for an alteration in PV-IR. Synaptic inhibition of the perforant path-dentate gyrus synapse evaluated in adult offspring, in vivo, revealed dose-dependent reductions in paired pulse depression indicative of a suppression of GABA-mediated inhibition. These data demonstrate that moderate degrees of thyroid hormone insufficiency during the early postnatal period permanently alters interneuron expression of PV and compromises inhibitory function in the hippocampus.

Amiodarone and thyroid hormone metabolism in the rat heart

1991 ◽  
Vol 125 (6) ◽  
pp. 675-679
Author(s):  
Liv S. Bjørn-Hansen Gøtzsche ◽  
Niels Boye
Keyword(s):  
Thyroid Hormone ◽  
Heart Muscle ◽  
High Dose ◽  
Dependent Manner ◽  
Hormone Metabolism ◽  
Tissue Concentrations ◽  
Cardiac Sarcolemma ◽  
Thyroid Hormone Metabolism ◽  
Liver And Kidney ◽  
Dose Dependent

Abstract. The effect of amiodarone on thyroid hormone metabolism in heart, muscle, liver and kidney was investigated. Rats were treated ip with a high (100 mg · kg−1 · day−1) or a low (50 mg · kg−1 · day−1) dose of amiodarone for 10 days. Serum T3 was dose-dependently depressed (mean 30 and 54% of controls, respectively, p<0.01). rT3 was elevated (to 663 and 313% of controls, p<0.01 and 0.05, respectively). Serum T4 was depressed only in the high-dose group (to mean 80%, p<0.05). Tissue concentrations of T3 in the heart and muscle from treated animals did not differ from controls, whereas liver and kidney T3 contents were markedly reduced in both groups (p<0.05). Heart T4 and rT3 were elevated to about 200% of controls (p<0.01 and 0.05, respectively). The same pattern was observed in the other tissues. Iodothyronine-5'-monodeiodinase activity was significantly depressed in all tissues; heart: 32 and 28% of controls (p<0.05); muscle: 36 and 49% (p<0.01); liver: 11 and 13% (p<0.01); kidney: 22 and 28% (p<0.01), respectively. In conclusion, amiodarone depresses iodothyronine-5'-monodeiodinase activity in the heart, muscle, liver and kidney in a dose-dependent manner, resulting in lowered T3 concentrations in the liver and kidney, whereas no reduction of tissue T3 content is observed in the heart and muscle. This may indicate that T3 from plasma may cross the cardiac sarcolemma without hindrance.

Thyroid hormones and brain development

1995 ◽  
Vol 133 (4) ◽  
pp. 390-398 ◽  
Author(s):  
Juan Bernal ◽  
Jacques Nunez
Keyword(s):  
Gene Expression ◽  
Cell Differentiation ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Brain Development ◽  
Neuronal Differentiation ◽  
Cell Biology ◽  
Physiological Role ◽  
Hormone Deficiency ◽  
Mammalian Brain

Bernal J, Nunez J. Thyroid hormones and brain development. Eur J Endocrinol 1995;133:390–8. ISSN 0804–4643 Thyroid hormone is a major physiological regulator of mammalian brain development. Cell differentiation, migration and gene expression are altered as a consequence of thyroid hormone deficiency or excess. The physiological role of thyroid hormone can perhaps be defined so as to ensure the timed coordination of different developmental events through specific effects on the rate of cell differentiation and gene expression. All triiodothyronine (T3) receptor isoforms are expressed in the brain and their spatial and temporal patterns of expression suggest unique and complementary functions for the different isoforms. Cell biology studies suggest a role for T3 and its receptors in oligodendroglial and neuronal differentiation and the control of cell death. Some of the effects on neuronal differentiation might be due to an action of thyroid hormone on the production of neurotropins and their receptors. In recent years a number of T3-dependent genes have been identified in the rat brain, such as myelin protein-encoding genes or specific neuronal genes, and thyroid hormone-responsive elements have been demonstrated in some of these genes. The identification of the gene network regulated by thyroid hormone during brain development, the elucidation of the mechanism of regulation and the clarification of the physiological roles of the regulated genes remain major goals for future studies. Jacques Nunez, INSERM U282. Hôpital Henri Mondor, 94010 Créteil, France

Mitogenic effects of thyroxine and TRH on thyrotrophs and somatotrophs of the anterior pituitary gland in thyroidectomized rats

1997 ◽  
Vol 154 (1) ◽  
pp. 149-153 ◽  
Author(s):  
A Quintanar-Stephano ◽  
C Valverde-R
Keyword(s):  
Thyroid Hormone ◽  
Synergistic Effect ◽  
Proliferative Response ◽  
Periodic Acid ◽  
Male Rats ◽  
High Dose ◽  
Dependent Manner ◽  
Simultaneous Administration ◽  
Mitotic Figures ◽  
Dose Dependent

Abstract The question of whether thyroxine (T4) and TRH have a mitogenic effect on pituitary thyrotrophs and somatotrophs in thyroidectomized rats was investigated. Mitoses were counted in hematoxylin–eosin-stained or periodic acid–Schiff–hematoxylin-stained pituitary slides or immunostained for TSH or GH using male rats thyroidectomized for 5 months. Ten days before they were killed groups of rats were injected with different doses of T4 (0·5, 3 or 10 μg i.m. every second day for 10 days), TRH alone (100 ng s.c. three times a day for 10 days), or T4 plus TRH (same doses as above). Mitoses (stopped with colchicine) were counted in 1 mm2 areas at a magnification of × 1000. In thyroidectomized rats, mitoses were not significantly increased and treatment with TRH or 0·5 μg T4 alone in thyroidectomized rats did not affect mitotic counts. In thyroidectomized rats treated with higher doses of T4, mitoses were increased in a dose-dependent fashion. Simultaneous administration of TRH and T4 had a significant synergistic effect on pituitary mitoses in a T4 dose-dependent manner. The treatments also had differential effects on the relative percentages of cellular types in mitosis. Thus, 60% somatotrophs and 12·5% thyrotrophs were found in the euthyroid group. In thyroidectomized and thyroidectomized plus TRH groups, no somatotrophs in mitosis were seen, while thyrotrophs were 28·5% and 33·3% respectively. In thyroidectomized rats treated with low doses of T4, somatotrophs and thyrotrophs in mitosis increased to 38·4% and 80% respectively and, with simultaneous administration of a low dose of T4 plus TRH, although less effective than T4 alone, mitosis increased in somatotrophs and thyrotrophs to 11·1% and 54·5% respectively. A high dose of T4 alone did not increase the mitotic figures in somatotrophs (38·8%), while it diminished the percentage of thyrotrophs to 25%. The administration of high doses of T4 plus TRH had an opposite effect on the mitotic figures of somatotrophs and thyrotrophs and thus the percentage of somatotrophs increased to 50% while thyrotrophs decreased to 5·5%. Ten days of treatment with T4 were insufficient to reverse the histology to euthyroidism. It can be concluded that in long-standing hypothyroidism: (1) thyroid hormone replacement elicits a dose-dependent and differential proliferative response on pituitary thyrotrophs and somatotrophs, (2) TRH is devoid of mitogenic effects when administered alone and (3) the proliferative response of somatotrophs to T4 is enhanced by its co-administration with TRH, suggesting a permissive and/or synergistic effect of the thyroid hormone and TRH. Journal of Endocrinology (1997) 154, 149–153

scholarly journals High-dose Glycerol Monolaurate Up-Regulated Beneficial Indigenous Microbiota without Inducing Metabolic Dysfunction and Systemic Inflammation: New Insights into Its Antimicrobial Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1981 ◽  
Author(s):  
Qiufen Mo ◽  
Aikun Fu ◽  
Lingli Deng ◽  
Minjie Zhao ◽  
Yang Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Systemic Inflammation ◽  
Body Weight Gain ◽  
High Dose ◽  
Dependent Manner ◽  
Glucose And Lipid Metabolism ◽  
Glycerol Monolaurate ◽  
Indigenous Microbiota ◽  
Anti Inflammatory ◽  
Dose Dependent

Glycerol monolaurate (GML) has potent antimicrobial and anti-inflammatory activities. The present study aimed to assess the dose-dependent antimicrobial-effects of GML on the gut microbiota, glucose and lipid metabolism and inflammatory response in C57BL/6 mice. Mice were fed on diets supplemented with GML at dose of 400, 800 and 1600 mg kg−1 for 4 months, respectively. Results showed that supplementation of GML, regardless of the dosages, induced modest body weight gain without affecting epididymal/brown fat pad, lipid profiles and glycemic markers. A high dose of GML (1600 mg kg−1) showed positive impacts on the anti-inflammatory TGF-β1 and IL-22. GML modulated the indigenous microbiota in a dose-dependent manner. It was found that 400 and 800 mg kg−1 GML improved the richness of Barnesiella, whereas a high dosage of GML (1600 mg kg−1) significantly increased the relative abundances of Clostridium XIVa, Oscillibacter and Parasutterella. The present work indicated that GML could upregulate the favorable microbial taxa without inducing systemic inflammation and dysfunction of glucose and lipid metabolism.

scholarly journals Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kathryn A. Ryan ◽  
Kevin R. Bewley ◽  
Susan A. Fotheringham ◽  
Gillian S. Slack ◽  
Phillip Brown ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Viral Rna ◽  
Dose Titration ◽  
High Dose ◽  
Lung Pathology ◽  
Upper Respiratory Tract ◽  
Virus Shedding ◽  
Upper Respiratory ◽  
Dose Dependent ◽  
Titration Study

AbstractThere is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5–15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

2021 ◽  
Vol 53 (04) ◽  
pp. 272-279
Author(s):  
Chaochao Ma ◽  
Xiaoqi Li ◽  
Lixin Liu ◽  
Xinqi Cheng ◽  
Fang Xue ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Pregnant Women ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Dynamic Change ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Free Thyroxine ◽  
Stimulating Hormone

AbstractThyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052–3.393 μIU/ml, 1.01–1.54 ng/dl, and 2.51–3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

scholarly journals Blood Micronutrient and Thyroid Hormone Concentrations in the Oldest-Old

2000 ◽  
Vol 85 (6) ◽  
pp. 2260-2265 ◽  
Author(s):  
Giovanni Ravaglia ◽  
Paola Forti ◽  
Fabiola Maioli ◽  
Barbara Nesi ◽  
Loredana Pratelli ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Oldest Old ◽  
Serum Zinc ◽  
Blood Levels ◽  
Elderly Age ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Plasma Retinol ◽  
Age Range

Several micronutrients are involved in thyroid hormone metabolism, but it is unclear whether their marginal deficits may contribute to the alterations in thyroid function observed in extreme aging. The relationships among blood concentrations of thyroid hormones and selenium, zinc, retinol, and α-tocopherol were studied in 44 healthy Northern Italian oldest-old subjects (age range, 90–107 yr), selected by the criteria of the SENIEUR protocol. Control groups included 44 healthy adult (age range, 20–65 yr) and 44 SENIEUR elderly (age range, 65–89 yr) subjects. Oldest-old subjects had higher TSH (P &lt; 0.01) and lower free T3 (FT3)/freeT4 (FT4) ratio, zinc, and selenium serum values (P &lt; 0.001) than adult and elderly control subjects. No significant difference was found for plasma retinol and α-tocopherol values. The associations between micronutrients and thyroid hormones were evaluated by multivariate analysis. In oldest-old subjects, plasma retinol was negatively associated with FT4 (P = 0.019) and TSH serum levels (P = 0.040), whereas serum zinc was positively associated with serum FT3 (P = 0.010) and FT3/FT4 ratio (P = 0.011). In younger subjects, no significant association was found among thyroid variables and micronutrients. In conclusion, blood levels of specific micronutrients are associated with serum iodothyronine levels in extreme aging.

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