A5035095061- Thyroid Disorders and Treatments
- Genetics and Neurodevelopmental Disorders
- Neuroscience of respiration and sleep
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Growth Hormone and Insulin-like Growth Factors
- Congenital heart defects research
- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Adipose Tissue and Metabolism
- CRISPR and Genetic Engineering
- Wnt/β-catenin signaling in development and cancer
- Renal and related cancers
- Thyroid Cancer Diagnosis and Treatment
- Memory and Neural Mechanisms
- Vestibular and auditory disorders
- Sirtuins and Resveratrol in Medicine
- Neonatal and fetal brain pathology
- Advanced MRI Techniques and Applications
- Cancer-related gene regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Receptor Mechanisms and Signaling
- Liver physiology and pathology
Instituto de Investigaciones Biomédicas Sols-Morreale
2006-2024
Universidad Autónoma de Madrid
2011-2024
Consejo Superior de Investigaciones Científicas
2009-2024
Unidades Centrales Científico-Técnicas
2024
Centro Nacional de Biotecnología
2024
Medical University of South Carolina
2024
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2024
LETO Maternity Hospital
2021
National and Kapodistrian University of Athens
2021
Instituto de Investigación de Enfermedades Raras
2020
Significance We show here that binding of the thyroid hormone triiodothyronine to receptors (TRs) antagonizes TGF-β/SMAD (mothers against decapentaplegic)-dependent transcription. Transcriptionally inactive TR mutants do not bind coactivators retained most capacity suppressing transactivation by TGF-β/SMAD, whereas selective mutations in DNA domain abolished this action. TGF-β is a major profibrogenic cytokine, and through transcriptional mechanism, hormone-bound TRs act as an endogenous...
dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function poorly understood. Here, we describe the generation characterization dkk3 mutant mice. dkk3-deficient mice are viable fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, most clinical chemistry parameters. Since Dkk3 was proposed to as thyroid hormone binding protein, have analyzed deiodinase activities, well levels. Mutant...
Abstract Activity‐dependent changes taking place at the hippocampal perforant pathway–dentate gyrus synapse during classical eyeblink conditioning were recorded in adult thyroidectomized (hypothyroid) and control (euthyroid) rats, animals treated with thyroid hormones 20 days after thyroidectomy (recovery rats). The aim was to determine contribution of consequences adult‐onset hypothyroidism both associative learning physiological potentiation synapses actual process alert behaving animals....
Background Thyroid hormones have a key role in both the developing and adult central nervous system skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but intracellular concentrations of 3,5,3′-triiodothyronine (T3; transcriptionally active hormone) muscle are modulated by activity type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations DIO2 gene previous studies young juvenile D2-knockout mice (D2KO) did not find gross alterations, possibly...
Background: Mutations in the thyroid hormone (TH) transporter monocarboxylate 8 (MCT8) lead to peripheral hyperthyroidism and profound psychomotor alterations humans. Mice lacking Mct8 present but no gross neurological abnormalities due brain compensatory mechanisms involving enzyme deiodinase type 2 (Dio2). Methods: Here we have analyzed endocrine neurologic phenotype of mice both Dio2 at three six months age. Thyroxine (T4) 3,5,3' triiodothyronine (T3) levels/content were measured by...
Monocarboxylate transporter 8 (MCT8) and organic anion polypeptide 1C1 (OATP1C1) are thyroid hormone (TH) transmembrane transporters that play an important role in the availability of TH for neural cells, allowing their proper development function. It is to define which cortical cellular subpopulations express those explain why MCT8 OATP1C1 deficiency humans leads dramatic alterations motor system. By means immunohistochemistry double/multiple labeling immunofluorescence adult human monkey...
The monocarboxylate transporter 8 (MCT8) plays a vital role in maintaining brain thyroid hormone homeostasis. This transmembrane is expressed at the barriers, as blood-brain barrier (BBB), and neural cells, being sole known hormone-specific to date. Inactivating mutations MCT8 gene (SLC16A2) cause Allan-Herndon-Dudley Syndrome (AHDS) or deficiency, rare X-linked disease characterized by delayed neurodevelopment severe psychomotor disorders. underlying pathophysiological mechanisms of AHDS...
Metainflammation is a chronic low-grade inflammatory state induced by obesity and associated comorbidities, including peripheral insulin resistance. Brown adipose tissue (BAT), therapeutic target against obesity, an sensitive to inflammation. Therefore, it necessary find strategies protect BAT the effects of inflammation in energy balance. In this study, we explored impact moderate sirtuin 1 (SIRT1) overexpression on sensitivity β-adrenergic responses brown adipocytes (BA) under...
Hypothyroidism is the most common hormonal disease in adults, which frequently accompanied by learning and memory impairments emotional disorders. However, deleterious effects of thyroid hormones deficiency on are poorly understood often underestimated. To evaluate consequences hypothyroidism memory, we have performed a classical Pavlovian fear conditioning paradigm euthyroid adult-thyroidectomized Wistar rats. In this experimental model, acquisition was not impaired, enhanced, extinction...
Thyroid hormones play an important role during the development and functioning of different sensory systems. In order to exert their actions, thyroid need access target cells through transmembrane transporter proteins, among which monocarboxylate 8 (MCT8) stands out for its pathophysiological relevance. Mutations in gene encoding MCT8 lead Allan-Herndon-Dudley syndrome (AHDS), a rare disease characterised by severe neuromotor cognitive impairments. The impact deficiency neurosensory capacity...
Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked disorder that causes severe neurological damage, for which there no effective treatment. AHDS due to inactivating mutations in the thyroid hormone transporter MCT8 impair entry of hormones into brain, resulting cerebral hypothyroidism. However, pathophysiology still not fully understood and this essential develop therapeutic strategies. Based on evidence suggesting deficit leads alterations astroglial cells, including gliosis, work, we...
Monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1) are thyroid hormones (TH) transmembrane transporters relevant for the availability of TH in neural cells, crucial their proper development function. Mutations MCT8 or OATP1C1 result severe disorders with dramatic movement disability related to alterations basal ganglia motor circuits. Mapping expression MCT8/OATP1C1 those circuits is necessary explain involvement control. We studied distribution...
The modulation of the host’s metabolism to protect tissue from damage induces tolerance infections increasing survival. Here, we examined role thyroid hormones, key metabolic regulators, in outcome malaria. Hypothyroidism confers protection experimental cerebral malaria by a disease mechanism. Hypothyroid mice display increased survival after infection with Plasmodium berghei ANKA, diminishing intracranial pressure and brain damage, without altering pathogen burden, blood-brain barrier...
Monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1) are thyroid hormone (TH) transmembrane transporters relevant for the availability of TH in neural cells, crucial their proper development function. Mutations MCT8 or OATP1C1 result severe disorders with dramatic movement disability related to alterations basal ganglia motor circuits. Mapping expression MCT8/OATP1C1 those circuits is necessary explain involvement control. We studied distribution both...
Abstract TaqIA is a polymorphism associated with addictions and dopamine-related traits. It located in the ankyrin repeat kinase domain containing 1 gene (ANKK1) nearby for dopamine D2 receptor (D2R). Since ANKK1 function unknown, TaqIA-associated traits have been explained only by differences D2R. Here we report studies mouse human brain using quantitative real-time PCR, Western blot, immunohistochemistry, flow cytometry. mRNA protein isoforms vary along neurodevelopment brain. In adult...
Inactivating mutations in the specific thyroid hormone transporter monocarboxylate 8 (MCT8) lead to an X-linked rare disease named MCT8 deficiency or Allan-Herndon-Dudley Syndrome. Patients exhibit a plethora of severe endocrine and neurological alterations, with no effective treatment for symptoms. An optimal mammalian model is essential explore pathological mechanisms potential therapeutic approaches. Here we have generated by CRISPR/Cas9 avatar mouse point mutation found two...
Introduction Pluripotent stem cells can be generated from somatic by the Yamanaka factors Oct4, Sox2, Klf4 and c-Myc. Methods Mouse embryonic fibroblasts (MEFs) were transduced with generation of induced pluripotent (iPSCs) was assessed formation alkaline phosphatase positive colonies, pluripotency gene expression embryod bodies formation. Results The thyroid hormone triiodothyronine (T3) enhances MEFs reprogramming. T3-induced iPSCs resemble in terms profile DNA methylation pattern genes,...
Deiodinases (D1, D2, and D3) are selenoproteins involved in thyroid hormone metabolism. Generation of the active T(3), from T(4), is carried out by D1 whereas D3 degrades both hormones. The identity cloned D2 as a selenoprotein well supported biochemical physiological data. However, an alternative view has proposed that type 2 deiodinase nonselenoprotein complex containing putative T(4) binding subunit called p29, with almost sequence Dickkopf protein Dkk3. To explore possible functional...
Abstract Background : Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked disorder that causes severe neurological damage, for which there no effective treatment. AHDS due to inactivating mutations in the thyroid hormone transporter MCT8 impair entry of hormones into brain, resulting cerebral hypothyroidism. However, pathophysiology still not fully understood and this essential develop therapeutic strategies. Based on evidence suggesting deficit leads alterations astroglial cells,...
Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | 1479-6848 (online)