A5076442919- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Genetics and Neurodevelopmental Disorders
- Sarcoma Diagnosis and Treatment
- Testicular diseases and treatments
- Neuroscience and Neuropharmacology Research
- Neuroscience of respiration and sleep
- Urologic and reproductive health conditions
- Neuropeptides and Animal Physiology
- Hypothalamic control of reproductive hormones
- Thyroid Cancer Diagnosis and Treatment
- Birth, Development, and Health
- Amino Acid Enzymes and Metabolism
- Genetic Syndromes and Imprinting
- Neuroinflammation and Neurodegeneration Mechanisms
- Erythrocyte Function and Pathophysiology
- Connective Tissue Growth Factor Research
- Cancer, Hypoxia, and Metabolism
- Microtubule and mitosis dynamics
- Neonatal and fetal brain pathology
- Adipose Tissue and Metabolism
- Estrogen and related hormone effects
- Regulation of Appetite and Obesity
- Immune Response and Inflammation
- Stress Responses and Cortisol
Essen University Hospital
2018-2025
University of Duisburg-Essen
2018-2025
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
2011-2023
Diabetes Australia
2023
Leibniz Institute of Environmental Medicine
2013-2021
University Hospital of Zurich
2013-2017
Leibniz Association
2007-2015
Immunologie-Zentrum Zürich
2013
Universitätsaugenklinik Magdeburg
2008-2011
Dorma (Germany)
2011
In humans, inactivating mutations in the gene of thyroid hormone transporter monocarboxylate 8 (MCT8; SLC16A2) lead to severe forms psychomotor retardation combined with imbalanced serum levels. The MCT8-null mice described here, however, developed without overt deficits but also exhibited distorted 3,5,3′-triiodothyronine (T3) and thyroxine (T4) levels, resulting increased hepatic activity type 1 deiodinase (D1). mutants’ brains, entry T4 was not affected, uptake T3 diminished. Moreover,...
Allan-Herndon-Dudley syndrome (AHDS), a severe form of psychomotor retardation with abnormal thyroid hormone (TH) parameters, is linked to mutations in the TH-specific monocarboxylate transporter MCT8. In mice, deletion Mct8 (Mct8 KO) faithfully replicates AHDS-associated endocrine abnormalities; however, unlike patients, these animals do not exhibit neurological impairments. While transport active TH (T3) across blood-brain barrier strongly diminished KO animals, prohormone (T4) can still...
Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions MALDI MSI data analysis are incomplete, require programming skills contain laborious manual steps, hindering broadly applicable, reproducible, high-throughput generate impactful biological...
Recent genetic analysis in several patients presenting a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels have revealed mutations or deletions the gene monocarboxylate transporter 8 (MCT8). Because vitro MCT8 functions as TH transporter, complex clinical picture these indicated an important role for TH-dependent processes brain development. To provide clue to cellular function brain, we studied expression mRNA murine central nervous system by...
Organic anion-transporting polypeptide 1c1 (Oatp1c1) (also known as Slco1c1 and Oatp14) belongs to the family of Oatp has been shown facilitate transport T(4). In rodent brain, Oatp1c1 is highly enriched in capillary endothelial cells choroid plexus structures where it may mediate entry T(4) into central nervous system. Here, we describe generation first analysis Oatp1c1-deficient mice. knockout (KO) mice were born with expected frequency, not growth retarded, developed without any overt...
Neocortex expansion during evolution is associated with the enlargement of embryonic subventricular zone, which reflects an increased self-renewal and proliferation basal progenitors. In contrast to human, vast majority mouse progenitors lack capacity, possibly due a process contacting lamina downregulation cell-autonomous production extracellular matrix (ECM) constituents. Here we show that targeted activation ECM receptor integrin αvβ3 on in neocortex promotes their expansion....
The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation TRH receptor 1 increases intracellular calcium tanycytes median eminence via Gαq/11 proteins. Activation pathways size...
Fourteen clinical trials have not shown a consistent benefit of combination therapy with levothyroxine (LT4) and liothyronine (LT3). Despite the publication these trials, is widely used patients reporting continue to generate patient physician interest in this area. Recent scientific developments may provide insight into inconsistency guide future studies.The American Thyroid Association (ATA), British (BTA), European (ETA) held joint conference on November 3, 2019 (live-streamed between...
The distribution of the recently discovered thyrotropin-releasing hormone (TRH) receptor subtype TRH-R2 was studied in rat brain, pituitary, and spinal cord by situ hybridization histochemistry compared with patterns other elements TRH signaling, namely TRH, TRH-R1, TRH-degrading ectoenzyme (TRH-DE). In contrast to very restricted mRNA expression TRH-R1 central nervous system, widely distributed highest transcript levels throughout thalamus, cerebral cerebellar cortex, medial habenulae,...
Transforming growth factor beta1 (TGFbeta1) is a pleiotropic cytokine with potent neurotrophic and immunosuppressive properties that upregulated after injury, but also expressed in the normal nervous system. In current study, we examined regulation of TGFbeta1 effects deletion on cellular response uninjured adult brain injured regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks birth TGFbeta1-deficient mice, this study was performed T- B-cell-deficient...
Abstract Brain microglia are related to peripheral macrophages but undergo a highly specific process of regional maturation and differentiation inside the brain. Here, we examined this deactivation morphological in cerebral cortex periventricular subcortical white matter, main “fountain microglia” site, during postnatal mouse development, 0–28 days after birth (P0–P28). Only matter not cortical exhibited strong expression typical activation markers alpha5, alpha6, alphaM, alphaX, beta2...
Monocarboxylate transporter 8 (MCT8) transports thyroid hormone (TH) across the plasma membrane. Mutations in MCT8 result Allan-Herndon-Dudley syndrome, comprising severe psychomotor retardation and elevated serum T3 levels. Because neurological symptoms are most likely caused by a lack of TH transport into central nervous system, administration analog that does not require for cellular uptake may represent therapeutic strategy. Here, we investigated potential biologically active metabolite...
In patients, inactivating mutations in the gene encoding thyroid hormone-transporting monocarboxylate transporter 8 (Mct8) are associated with severe mental and neurological deficits disturbed hormone levels. The latter phenotype characterized by high T3 low T4 serum concentrations is replicated Mct8 knockout (ko) mice, indicating that MCT8 deficiency interferes production and/or metabolism. Our studies of ko mice indeed revealed increased thyroidal without overt signs a hyperactive gland....
The monocarboxylate transporter 8 (MCT8) plays a critical role in mediating the uptake of thyroid hormones (THs) into brain. In patients, inactivating mutations MCT8 gene are associated with severe form psychomotor retardation and abnormal serum TH levels. Here, we evaluate therapeutic potential analog 3,5,3′,5′-tetraiodothyroacetic acid (tetrac) as replacement for T4 brain development. Using COS1 cells transfected deiodinase constructs, could show that tetrac, albeit not being transported...
The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with well-established TH Mct8. Because Mct8 deficiency is associated distinct tissue-specific alterations in metabolism, we speculated that inactivation may compromise homeostasis as well. However, analysis knockout (ko) mice revealed normal serum levels tissue content contrast to ko are characterized by high T3, low...
Sulforhodamine 101 (SR101) is widely used for astrocyte identification, though the labeling mechanism remains unknown and efficacy of in different brain regions heterogeneous. By combining region-specific isolation astrocytes followed by transcriptome analysis, two-photon excitation microscopy, mouse genetics, we identified thyroid hormone transporter OATP1C1 as SR101-uptake hippocampus cortex.
Thyroid hormones (TH) are essential for brain development and function. The TH transporters monocarboxylate transporter 8 (MCT8) organic anion transporter1 C1 (OATP1C1) facilitate the transport of across blood-brain barrier into glia neuronal cells in brain. Loss MCT8 function causes Allan-Herndon-Dudley syndrome (AHDS, OMIM 300523) characterized by severe intellectual motor disability due to cerebral hypothyroidism. Here, first patient with loss OATP1C1 is described. a 15.5-year-old girl...
A genetic deficiency of the solute carrier monocarboxylate transporter 8 (MCT8), termed Allan-Herndon-Dudley syndrome, is an important cause X-linked intellectual and motor disability. MCT8 transports thyroid hormones across cell membranes. While hormone analogues improve peripheral changes deficiency, no treatment neurological symptoms available so far. Therefore, we tested a gene replacement therapy in Mct8- Oatp1c1-deficient mice as well-established model disease. Here, report that...
The thyroid hormone l-3,3',5-triiodothyronine (T3) plays an important role during cerebellar development. Perinatal T3 deficiency leads to severe cellular perturbations, among them a striking reduction in the growth and branching of Purkinje cell dendritic arborization. molecular mechanisms underlying these effects are poorly understood. Despite well documented broad expression receptors (TRs), analysis different TR-deficient mice has failed provide detailed information about function...
Thyroid hormones are essential for a variety of developmental and metabolic processes. Congenital hypothyroidism (CHT) results in severe defects the development different tissues, particular brain. As an animal model CHT, we studied Pax8(-/-) mice, which born without thyroid gland. We determined expression iodothyronine deiodinase D1 liver kidney, D2 brain pituitary, D3 brain, as well serum T(4), T(3), rT(3) levels vs. control mice during first 3 wk life. In T(4) T(3) were undetectable on...