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1.
Mol Cell Neurosci ; 76: 1-10, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27501773

RESUMO

Thyroid hormones (THs) regulate adult hippocampal neurogenesis, a process that involves both cell populations that dynamically switch between pools of proliferative and quiescent cells, and cells that definitely leave the cell cycle to maturate into granular neurons. This investigation was carried out to determine the role of THs on the mitotic activity of specific proliferative cell populations and the preservation of non-proliferative cells participating in the neurogenic process of the dentate gyrus (DG) of the hippocampus. Hypothyroidism was induced in male adult Wistar rats with methimazole for 28days. We quantified the total number of proliferative cells (BrdU+), proliferative type 1 (BrdU+/GFAP+), and 2b and 3 (BrdU+/DCX+) cells. Early non-proliferative cells (BrdU-/DCX+ cells lacking dendritic process), postmitotic neuroblasts (Tuj 1+ cells lacking dendritic process), and immature granular neurons (IGN; DCX+ or Tuj 1+ and the presence of dendritic processes into granular or molecular layer) were also included. The evidence showed that the proliferation of Type 1, 2b and 3 cells is not modified by hypothyroidism. In contrast, hypothyroidism reduced the number of early non-proliferative cells and also leads to a decrement in the number of IGN. Our results show that proliferative cells of the DG are not sensitive to thyroid perturbations. However, THs are essential to preserve cell populations that leave the cell cycle in the DG of the hippocampus.


Assuntos
Giro Denteado/citologia , Neurogênese , Neurônios/citologia , Hormônios Tireóideos/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proliferação de Células , Giro Denteado/metabolismo , Proteína Duplacortina , Masculino , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Wistar , Hormônios Tireóideos/sangue
2.
J Neuroendocrinol ; 27(1): 8-19, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25327136

RESUMO

Thyroid hormone (TH) is essential for a number of physiological processes and is particularly critical during nervous system development. The hippocampus is strongly implicated in cognition and is sensitive to developmental hypothyroidism. The impact of TH insufficiency in the foetus and neonate on hippocampal synaptic function has been fairly well characterised. Although adult onset hypothyroidism has also been associated with impairments in cognitive function, studies of hippocampal synaptic function with late onset hypothyroidism have yielded inconsistent results. In the present study, we report hypothyroidism induced by the synthesis inhibitor propylthiouracil (10 p.p.m., 0.001%, minimum of 4 weeks), resulted in marginal alterations in excitatory postsynaptic potential (EPSP) and population spike (PS) amplitude in the dentate gyrus measured in vivo. No effects were seen in tests of short-term plasticity, and a minor enhancement of long-term potentiation of the EPSP slope was observed. The most robust synaptic alteration evident in hypothyroid animals was an increase in synaptic response latency, which was paralleled by a failure to maintain normal body temperature under anaesthesia, despite warming on a heating pad. Latency shifts could be reversed in hypothyroid animals by increasing the external heat source and, conversely, synaptic delays could be induced in control animals by removing the heat source, with a consequent drop in body and brain temperature. Thermoregulation is TH- dependent, and anaesthesia necessary for surgical procedures posed a thermoregulatory challenge that was differentially met in control and hypothyroid animals. Minor increases in field potential EPSP slope, decreases in PS amplitudes and increased latencies are consistent with previous reports of hypothermia in naive control rats. We conclude that failures in thyroid-dependent temperature regulation rather than direct action of TH in synaptic physiology are responsible for the observed effects. These findings stand in contrast to the synaptic impairments observed in adult offspring following developmental TH insufficiency, and emphasise the need to control for the potential unintended consequences of hypothermia in the interpretation of hypothyroid-induced changes in physiological systems, most notably synaptic transmission.


Assuntos
Anestesia/efeitos adversos , Giro Denteado/fisiopatologia , Hipocampo/fisiopatologia , Hipotermia/fisiopatologia , Hipotireoidismo/fisiopatologia , Idade de Início , Animais , Potenciais Pós-Sinápticos Excitadores , Hipotermia/induzido quimicamente , Masculino , Propiltiouracila/administração & dosagem , Ratos , Ratos Long-Evans
3.
Oxid Med Cell Longev ; 2013: 218145, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24386502

RESUMO

Reactive oxygen species (ROS) are oxidizing agents amply implicated in tissue damage. ROS production is inevitably linked to ATP synthesis in most cells, and the rate of production is related to the rate of cell respiration. Multiple antioxidant mechanisms limit ROS dispersion and interaction with cell components, but, when the balance between ROS production and scavenging is lost, oxidative damage develops. Many traits of aging are related to oxidative damage by ROS, including neurodegenerative diseases. Thyroid hormones (THs) are a major factor controlling metabolic and respiratory rates in virtually all cell types in mammals. The general metabolic effect of THs is a relative acceleration of the basal metabolism that includes an increase of the rate of both catabolic and anabolic reactions. THs are related to oxidative stress not only by their stimulation of metabolism but also by their effects on antioxidant mechanisms. Thyroid dysfunction increases with age, so changes in THs levels in the elderly could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear. In this review, we analyze the participation of thyroid hormones on ROS production and oxidative stress, and the way the changes in thyroid status in aging are involved in neurodegenerative diseases.


Assuntos
Degeneração Neural/patologia , Estresse Oxidativo/efeitos dos fármacos , Hormônios Tireóideos/farmacologia , Envelhecimento/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Humanos , Degeneração Neural/metabolismo , Espécies Reativas de Oxigênio/metabolismo
4.
J Neurosci Res ; 90(4): 905-12, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22184033

RESUMO

Thyroid hormones modulate the physiology of the hippocampus in humans, where glutamate plays an important role as neurotransmitter. The aim of this work was to study the effect of hypothyroidism on hippocampal glutamate extracellular levels, release, uptake, and synthesis. The effects of PDC (a glutamate transporter inhibitor) and ouabain (a Na(+) /K(+) -ATPase inhibitor) infusion on microdialysate glutamate and aspartate levels of CA3 hippocampal region were evaluated. Animals were assigned to one of the following groups: hypothyroid group (Hyp), receiving methimazole (anantithyroid drug); replacement group (Hyp + T(4) ), receiving antithyroid treatment plus thyroxine; and euthyroid control group (Eut). Dialysate fractions were collected every 15 min to determine basal glutamate levels for 1 hr. Then, PDC (10 mM) or ouabain (100 µM) was infused for 30 min. Results showed lower glutamate and aspartate basal levels in Hyp than in Eut groups. PDC infusion increased amino acids levels in all groups, whereas ouabain infusion increased glutamate and aspartate levels only in the Eut group. The infusion of tetrodotoxin (TTX; a voltage-gated sodium channel inhibitor) prevented the glutamate increase in euthyroid rats. The Hyp + T(4) group showed glutamate levels similar to those found in the Eut group. Additionally, glutaminase activity in hippocampus was lower in the Hyp group than in the Eut or Hyp + T(4) group. Results suggest that high-affinity glutamate transporters are not altered by hypothyroidism; however, decreased hypotyroidism reduced vesicular glutamate release in the CA3-hippocampal region as a consequence of diminished glutamate synthesis.


Assuntos
Região CA3 Hipocampal/citologia , Ácido Glutâmico/metabolismo , Hipotireoidismo/metabolismo , Ouabaína/farmacologia , Sinapses/efeitos dos fármacos , Análise de Variância , Animais , Antitireóideos/efeitos adversos , Ácido Aspártico/metabolismo , Região CA3 Hipocampal/efeitos dos fármacos , Região CA3 Hipocampal/metabolismo , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Glutamato-Amônia Ligase/metabolismo , Glutaminase/metabolismo , Hipotireoidismo/induzido quimicamente , Masculino , Metimazol/efeitos adversos , Microdiálise , Inibidores da Captação de Neurotransmissores/farmacologia , Ratos , Ratos Wistar , Tiroxina/sangue , Tiroxina/farmacologia
5.
Neuropharmacology ; 44(1): 111-6, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12559128

RESUMO

The effects of a mild hypothyroidism condition on benzodiazepine (BDZ) and mu opioid receptor levels was investigated. Female Wistar rats were randomly divided into two groups: 1) hypothyroid rats (n=7), which received methimazole (60 mg/kg per day) in drinking water for four weeks, and 2) euthyroid rats (n=8), which drank only tap water. Animals were sacrificed and their brains were used for autoradiography experiments. When compared to the euthyroid group, the hypothyroid group presented reduced benzodiazepine receptor binding in medial amygdala (24%) and high mu-receptor levels in frontal (25%), sensorimotor (65%) and temporal (29%) cortices, basolateral amygdala (50%) and ventroposterior thalamic nucleus (49%). The present data suggest that alterations in BDZ and mu-receptor binding could be associated with the higher excitability observed in animals with triiodothyronine (T(3)) deficiency.


Assuntos
Encéfalo/metabolismo , Receptores de GABA-A/metabolismo , Receptores Opioides mu/metabolismo , Tiroxina/sangue , Tri-Iodotironina/deficiência , Animais , Antitireóideos , Autorradiografia , Ligação Competitiva , Ala(2)-MePhe(4)-Gly(5)-Encefalina/metabolismo , Feminino , Flunitrazepam/metabolismo , Agonistas GABAérgicos/metabolismo , Agonistas de Receptores de GABA-A , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/metabolismo , Metimazol , Ensaio Radioligante , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores Opioides mu/agonistas , Tri-Iodotironina/sangue
7.
Life Sci ; 69(22): 2575-82, 2001 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-11712661

RESUMO

Lidocaine, a local anesthetic, produces seizures by unknown central mechanisms. The objective of this study was to investigate the effect of cellular metabolism alteration, by changing thyroid hormones levels, on susceptibility to lidocaine-kindling. Lidocaine was administered daily (60 mg/Kg x day, i.p.) to rats treated with thyroxine (300 microg/Kg x day) or methimazole (60 mg/Kg day), dissolved in drinking water. After the 18th lidocaine administration, the cumulative percent of animals convulsed was higher (100%) for the methimazole-treated group and lower (20%) for the thyroxine-treated group, compared to the control group (40%). The results suggest that susceptibility to lidocaine-kindling depends on neuronal metabolism, which probably affects monoamines uptake mechanisms.


Assuntos
Excitação Neurológica/fisiologia , Hormônios Tireóideos/fisiologia , Análise de Variância , Anestésicos Locais/efeitos adversos , Anestésicos Locais/farmacologia , Animais , Excitação Neurológica/efeitos dos fármacos , Lidocaína/efeitos adversos , Lidocaína/farmacologia , Modelos Animais , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/metabolismo
8.
Life Sci ; 66(21): 2013-21, 2000 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-10823341

RESUMO

It is known that lactation induces a mild hypothyroid state in rats and other mammals while thyroid hormone administration increases milk secretion in ruminants. The aim of this study was to investigate the effects of a moderate dose of 3,5,3'-triiodothyronine (T3), administered to rat dams during lactation on pups' growth and milk yield and composition. Primiparous Wistar rats with litters adjusted to 10 pups per dam received either tap water or T3 (75 microg/kg x day) in their drinking water from parturition till weaning. Food and water intake of dams and body weight of dams and pups were measured daily. In other groups of rats with similar treatments, milk yield of dams, macronutrient milk composition, and mammary arteriovenous differences for triglycerides (TG) and glucose were also determined. Dams treated with T3 ingested more food and their pups gained more weight than controls. Milk yield, milk TG concentration and glucose extraction by mammary glands were also higher in T3 treated dams. The results show that compensation of the mild hypothyroidism of the lactating rat may contribute to an increase in milk production and lipid levels, leading to an increase in growth of pups.


Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Lactação/efeitos dos fármacos , Leite/efeitos dos fármacos , Triglicerídeos/metabolismo , Tri-Iodotironina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Leite/fisiologia , Ratos , Ratos Wistar , Tri-Iodotironina/administração & dosagem
10.
Horm Metab Res ; 29(11): 577-9, 1997 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9479559

RESUMO

The effects of 3,5,3'-triiodothyronine (T3) levels on threshold, latency and duration of pentylenetetrazole-induced seizures were tested in rats treated with thyroxine (300 micrograms/kg.day, N = 9) or methimazole (60 mg/kg.day, N = 5) dissolved in drinking water. Compared to controls (N = 7), methimazole treatment reduced T3 levels (45.4 +/- 2.0 vs. 33.0 +/- 4.8 ng/dl) and increased seizure duration (36.2 +/- 22.4 vs. 289.6 +/- 24.4 s) and threshold (29.0 +/- vs. 45.5 mg/kg). Thyroxine treatment increased T3 levels (45.4 +/- 2.0 vs. 67.7 +/- 4.8 ng/dl), but had no significant effect on seizures.


Assuntos
Convulsivantes/administração & dosagem , Pentilenotetrazol/administração & dosagem , Convulsões/induzido quimicamente , Tri-Iodotironina/deficiência , Animais , Antitireóideos/farmacologia , Colo/fisiopatologia , Overdose de Drogas , Masculino , Metimazol/farmacologia , Ratos , Ratos Wistar , Convulsões/fisiopatologia , Temperatura , Tiroxina/sangue , Tiroxina/efeitos dos fármacos , Tiroxina/farmacologia , Fatores de Tempo , Tri-Iodotironina/sangue , Tri-Iodotironina/efeitos dos fármacos
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