A5058663471- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Neuroscience of respiration and sleep
- Genomics and Rare Diseases
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Retinoids in leukemia and cellular processes
- Estrogen and related hormone effects
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Congenital heart defects research
- MicroRNA in disease regulation
- Genomic variations and chromosomal abnormalities
- Hypothalamic control of reproductive hormones
- Axon Guidance and Neuronal Signaling
- Nuclear Receptors and Signaling
- Ion channel regulation and function
- Birth, Development, and Health
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Thyroid Cancer Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Genetic Associations and Epidemiology
Centre for Biomedical Network Research on Rare Diseases
2012-2024
Instituto de Salud Carlos III
2008-2024
Centro de Investigación Biomédica en Red
2011-2024
Instituto de Investigación de Enfermedades Raras
2008-2023
Universidad Autónoma de Madrid
2001-2020
Consejo Superior de Investigaciones Científicas
2002-2020
Instituto de Investigaciones Biomédicas Sols-Morreale
1994-2015
Medical Research Network
2012
Karolinska Institutet
2002
Fundación Ramón Domínguez
1997
The hypocretins (hcrts), also known as orexins, are two recently identified excitatory neuropeptides that in rat produced by ∼1200 neurons whose cell bodies located the lateral hypothalamus. hypocretins/orexins have been implicated regulation of rapid eye movement (REM) sleep and pathophysiology narcolepsy. In present study, we investigated whether locus coeruleus (LC), a structure receiving dense hcrtergic innervation, which is quiescent during REM sleep, might be target for hcrt to...
Thyroid hormone (T3) controls critical aspects of cerebellar development, such as migration postmitotic granule cells and terminal differentiation Purkinje cells. T3 acts through nuclear receptors (TR) two types, TRalpha1 TRbeta, that either repress or activate gene expression. We have analyzed the structure developing mice lacking isoform, which normally accounts for about 80% in cerebellum. Contrary to what was expected, cell were normal mutant mice. Even more striking fact when neonatal...
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...
To identify thyroid hormone-sensitive neuronal populations in the forebrain, we studied effects of hormone deficiency and replacement on expression RC3 messenger RNA (mRNA) rat brain by situ hybridization. RC3/neurogranin is a brain-specific, calmodulin-binding, protein kinase C substrate that has been implicated postsynaptic events involving calcium as second messenger. We have previously shown mRNA concentrations are dependent developing adult rats. In normal rats, occurs two phases....
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...
The effects of thyroid hormone on brain development and function are largely mediated by the binding 3,5,3′-triiodo-L-thyronine (T3) to its nuclear receptors (TR) regulate positively or negatively gene expression. We have analyzed quantitative polymerase chain reaction effect T3 primary cultured cells from embryonic mouse cerebral cortex, expression Hr, Klf9, Shh, Dio3, Aldh1a1, Aldh1a3. In particular we focused receptor specificity, crosstalk between T3, retinoic acid dexamethasone. To...
Thyroid hormones, thyroxine, and triiodothyronine (T3) are crucial for cerebral cortex development acting through regulation of gene expression. To define the transcriptional program under T3 regulation, we have performed RNA-Seq T3-treated untreated primary mouse cerebrocortical cells. The expression 1145 genes or 7.7% expressed was changed upon addition, which 371 responded to in presence cycloheximide indicating direct regulation. results were compared with available transcriptomic...
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 regulate brain development and function through the control of gene expression, mediated by binding T3 to nuclear receptors. Brain concentration is tightly controlled homeostatic mechanisms regulating transport metabolism T4 T3. We have examined role inactivating enzyme type 3 deiodinase (D3) in regulation 43 thyroid hormone-dependent genes cerebral cortex 30-d-old mice. D3 inactivation increased slightly expression two 22 positively regulated significantly decreased seven...
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...
The knowledge of the genetic variability local population is utmost importance in personalized medicine and has been revealed as a critical factor for discovery new disease variants. Here, we present Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes exomes unrelated individuals. This database generated collaborative crowdsourcing effort collecting sequencing data produced by genomic projects other purposes. Sequences have grouped ICD10 upper...
NRGN is the human homolog of neuron-specific rat RC3/neurogranin gene. This gene encodes a postsynaptic 78-amino acid protein kinase substrate that binds calmodulin in absence calcium, and has been implicated dendritic spine formation synaptic plasticity. In brain RC3 under thyroid hormone control specific neuronal subsets both developing adult animals. To evaluate whether also target we have searched for T3-responsive elements cloned genomic fragments spanning whole Labeled DNA were...
Abstract Thyroid hormone influences brain maturation through interaction with nuclear receptors and regulation of gene expression. Their role on astrocyte remains unclear. We have analyzed the thyroid in rat cerebellar by comparing sequential patterns intermediate filament expression normal hypothyroid animals. During development astroglial cells sequentially express nestin, vimentin, glial fibrillary acidic protein. Differentiated astrocytes appeared superior medullary vellum postnatal day...
Thyroid hormones have important actions in the developing central nervous system. We describe here a novel action of thyroid hormone and its nuclear receptors on maturation cerebellar gamma-aminobutyric acid (GABA)-ergic interneurons from their precursor cells. In rats, density GABAergic terminals cerebellum was decreased by hypothyroidism, as shown immunohistochemistry for GABA transporter GAT-1. This due, at least partially, to number cells, because Golgi II cells internal granular layer...
Abstract The effects of thyroid hormones (THs) on brain development and function are largely mediated by the control gene expression. This is achieved binding genomically active T3 to transcriptionally nuclear TH receptors (TRs). TRs can either induce or repress transcription. In hypothyroidism, reduction lowers expression a set genes, positively regulated increases negatively genes. Two mechanisms may account for effect hypothyroidism genes directly T3: first, loss signaling TR...
Astrocytes mediate the action of thyroid hormone in brain on other neural cells through production active triiodothyronine (T3) from its precursor thyroxine. T3 has also many effects astrocytes vivo and culture, but whether these actions are directly mediated by transcriptional regulation is not clear. In this work, we have analyzed genomic response to cultured isolated postnatal mouse cerebral cortex using RNA sequencing. Cultured express relevant genes metabolism encoding type 2 deiodinase...