A5077712842- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Neuroscience of respiration and sleep
- Genetics and Neurodevelopmental Disorders
- Adipose Tissue and Metabolism
- Neonatal Health and Biochemistry
- Genetic Syndromes and Imprinting
- Hippo pathway signaling and YAP/TAZ
- Higher Education Teaching and Evaluation
- Microtubule and mitosis dynamics
- Ion channel regulation and function
- Fungal and yeast genetics research
- Health and Medical Education
- Regulation of Appetite and Obesity
- Adenosine and Purinergic Signaling
- Peroxisome Proliferator-Activated Receptors
- Adipokines, Inflammation, and Metabolic Diseases
- Cardiovascular Disease and Adiposity
- Radiopharmaceutical Chemistry and Applications
- Thyroid Cancer Diagnosis and Treatment
- Estrogen and related hormone effects
- Neonatal and fetal brain pathology
- Axon Guidance and Neuronal Signaling
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
Instituto de Investigaciones Biomédicas Sols-Morreale
2007-2024
Universidad Complutense de Madrid
2019-2024
Consejo Superior de Investigaciones Científicas
2012-2024
Universidad Autónoma de Madrid
2011-2024
Centro Nacional de Biotecnología
2024
Medical University of South Carolina
2024
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2024
Instituto de Neurociencias
2012-2022
Benemérita Universidad Autónoma de Puebla
2021
Czech Academy of Sciences, Institute of Physiology
2021
Mutations of the gene expressing plasma membrane transporter for thyroid hormones MCT8 (SLC16A2) in humans lead to altered hormone levels and a severe neurodevelopmental disorder. Genetically engineered defect Mct8 mice leads similar abnormalities but no obvious impairment brain development or function. In this work we studied relative role blood-brain barrier neuronal cell restricted access T3 target neurons. To end compared effects low doses T4 on cerebellar structure expression wild-type...
Mutations in the MCT8 (SLC16A2) gene, encoding a specific thyroid hormone transporter, cause an X-linked disease with profound psychomotor retardation, neurological impairment, and abnormal serum levels. The nature of central nervous system damage is unknown.The objective study was to define neuropathology syndrome by analyzing brain tissue sections from MCT8-deficient subjects.We analyzed 30th gestational week male fetus 11-year-old boy as controls, 28th female fetuses, respectively,...
Thyroid hormones influence brain development through the control of gene expression. The concentration active hormone T3 in depends on transport blood-brain barrier, mediated part by monocarboxylate transporter 8 (Mct8/MCT8) and activity type 2 deiodinase (D2) generating from T4. relative roles each these pathways regulation expression is not known. To shed light this question, we analyzed thyroid hormone-dependent cerebral cortex mice with inactivated Mct8 (Slc16a2) Dio2 genes, alone or...
Abstract Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause Allan-Herndon-Dudley syndrome, an X-linked syndrome severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 T3), is likely caused by lack T3 transport to neurons during critical periods fetal brain development. To evaluate role in hormone action we administered T4 or thyroidectomized pregnant dams treated with methyl-mercapto-imidazol produce maternal hypothyroidism. Gene...
Thyroid hormones have profound effects on mood and behavior, but the molecular basis of thyroid hormone action in adult brain is relatively unknown. In particular, few hormone-dependent genes been identified despite extensive work carried out developing brain. this we performed global analysis gene expression rat striatum search for genomic changes taking place after administration T(3) to hypothyroid rats. The was administered two different schedules: 1) a single, large dose 25 microg per...
Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during second trimester, a period high sensitivity to thyroid hormones. In rat, equivalent is last quarter pregnancy. However, little known about hormone action fetal brain, and rodents, most hormone-regulated genes have been identified postnatal period. To identify potential targets we induced maternal...
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...
The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature neonates. However, although BAT has been studied infants for more than century, knowledge about its physiological features at this stage life is rather limited. This mainly due to lack appropriate investigation methods, ethically suitable Here, we have applied non-invasive infrared thermography (IRT) investigate neonatal activity. Our data show correlates with body and mild cold...
Transfer cells have specializations that facilitate the transport of solutes across plant exchange surfaces. ZmMRP-1 is a maize (Zea mays) endosperm transfer cell-specific transcriptional activator plays central role in regulatory pathways controlling cell differentiation and function. The present work investigates signals expression through production transgenic lines maize, Arabidopsis, tobacco barley containing ZmMRP-1promoter:GUS reporter constructs. GUS signal predominantly appeared...
Thyroid hormone analogs with selective actions through specific thyroid receptor (TR) subtypes are of great interest. They might offer the possibility mimicking physiological subtype or tissue specificity therapeutic aims. also pharmacological tools to dissect biochemical pathways mediated by subtypes, in a complementary way mouse genetic modifications. In this work, we studied vivo activity developing rats two agonists, TRβ-selective GC-24 and TRα-selective CO23. Our principal goal was...
Thyroid hormones act directly on gene transcription in the post-natal developing cerebellum, controlling neuronal, and glial cell differentiation. We have combined three experimental approaches to identify target genes that are underlying this phenomenon: 1) a microarray analysis of expression hormone responsive cerebellum Pax8−/− mice, transgenic mouse model congenital hypothyroidism; 2) similar primary culture neurons; 3) bioinformatics screen conserved putative-binding sites genome. This...
During nervous system development different cell-to-cell communication mechanisms operate in parallel guiding migrating neurons and growing axons to generate complex arrays of neural circuits. How such a works coordination is not well understood. Cross-regulatory interactions between signalling pathways redundancy them can increase precision fidelity guidance systems. Immunoglobulin superfamily proteins the NCAM L1 families couple specific substrate recognition cell adhesion with activation...
In response to peripheral nerve injury, Schwann cells adopt a migratory phenotype and modify the extracellular matrix make it permissive for cell migration axonal re-growth. Uridine 5′-triphosphate (UTP) other nucleotides are released during injury activate purinergic receptors expressed on surface, but little is known about involvement of purine signalling in wound healing. We studied effect UTP Schwannoma closure intracellular signaling pathways involved. found that treatment induced...
Background: Loss of function mutations in the thyroid hormone (TH)-specific cell membrane transporter, monocarboxylate transporter 8 (MCT8), lead to profound psychomotor retardation and abnormal TH serum levels, with low thyroxine (T4) high triiodothyronine (T3). Several studies point impaired transport across brain barriers as a crucial pathophysiological mechanism resulting cerebral hypothyroidism. Treatment options for MCT8-deficient patients are limited focused on overcoming barriers....
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...
Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is specific thyroid hormone (T4 T3) patients also present unusual abnormalities in serum profile concentrations due to altered secretion metabolism T4 T3. Given role hormones brain development, it thought that impairment restricted transport target neurons. In this work we have investigated cerebral mice with Mct8 deficiency. Adult male were infused for 30...
Thyroid hormones (THs) play a major role regulating energy balance and brown adipose tissue (BAT) thermogenesis, as well body temperature, shown in hyperthyroid patients. However, the current landscape of preclinical thyroid hormone models is complex. For example, while rats become catabolic after TH administration, mice gain weight; so, these differences species need to be analyzed detail specially whether temperature could factor. Here, we aimed investigate effect environmental on those...
Patients lacking the thyroid hormone (TH) transporter MCT8 present abnormal serum levels of TH: low thyroxine and high triiodothyronine. They also have severe neurodevelopmental defects resulting from cerebral hypothyroidism, most likely due to impaired TH transport across brain barriers. The use analogs, such as triiodothyroacetic acid (TRIAC), that can potentially access in absence restore at least a subset actions could improve neurological these patients. We hypothesized direct...
Loss of function mutations in the gene encoding thyroid hormone transporter monocarboxylate 8 (MCT8) lead to severe neurodevelopmental defects humans associated with a specific phenotype manifesting high serum 3,5,3’-triiodothyronine (T3) and low thyroxine (T4) levels. Patients present paradoxical state peripheral hyperthyroidism brain hypothyroidism, this last one most likely arising from impaired transport across barriers. The administration hormones by delivery pathways that bypass...
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...
How cell to interactions control local tissue growth attain a species-specific organ size is central question in developmental biology. The Drosophila Neural Cell Adhesion Molecule, Fasciclin 2, expressed during the development of neural and epithelial organs. 2 homophilic-interaction protein that shows moderate levels expression proliferating epithelia high differentiating non-proliferative cells imaginal discs. Genetic mosaic analyses reveal autonomous requirement promote proliferation...