Head


Heike Heuer
Heike Heuer

Postdocs

Sigrun Horn

PhD Students

Claudia Groba

Steffen Mayerl

Julia Müller

N. N. ( » Job offer)

Diploma Students

Technicians

Sabine Landmann

Maik Baldauf (histology)

Katrin Buder (histology)

Guests

Isabell Börger (apprentice)



Former Lab Members

Marija Trajkovic-Arsic


Interested in joining our group? For further information please contact
hheuer at fli-leibniz.de.

 

Heuer Laboratory

Neuroendocrinology

Thyroid hormones and brain functions

Thyroid hormones (TH) are essential for proper brain development and the metabolic homeostasis of the organism. While in the adult TH deficiency is associated with dementia, neurological symptoms and depression, untreated congenital hypothyroidism leads to irreversible brain damage characterized by mental retardation, deafness and severe motor defects. Surprisingly, the molecular mechanisms underlying these deficits are poorly understood as yet. Our aim is to define the mechanisms of TH action in the developing as well as in the adult brain.

 

single Purkinje cell

 

» This figure depicts a single Purkinje cell in an organotypic slice culture after transfection with a plasmid coding for green fluorescent protein (GFP). Note the pronounced organisation of the dendritic tree.

 

 

 

 

Projects

  • Thyroid hormone action during cerebellar development

We are particularly interested in studying the role of thyroid hormone during the development of the cerebellum, a brain region important for locomotor activity. A major focus of our research is to analyse how thyroid hormone deficiency affects the Purkinje cell, the principle neuron of the cerebellum as well as the Bergmann glia, a specialized radial glia cell.

 

Purkinje cells

Purkinje cells kept for 14 days in culture in the absence or presence of TH were stained with an antibody against Calbindin. Note the TH induced dramatic increase in Purkinje cell dendritic branching.

To unravel the molecular events we are using primary neuronal cell cultures as well as organotypic culture in order to identify growth factors and signalling cascades that are direct targets of TH action. To this aim, we are also analyzing genetically modified mice that are athyroid since they do not develop a thyroid gland or are deficient in specific thyroid hormone receptor isoforms.

 

  • Physiological role of thyroid hormone transporter MCT8

Thyroid hormone deficiency during embryonic development caused by severe maternal hypothyroidism leads to severe forms of neurological cretinism. Alternatively, this syndrome can be provoked by an impaired TH transport across cell membranes that prevents intracellular TH action. The monocarboxylate transporter MCT8 was recently identified as a very specific and active thyroid hormone transporter. Furthermore, patients suffering from a severe form of X-linked psychomental retardation in combination with abnormal thyroid hormone levels were shown to carry inactivating mutations or deletions in the gene of the monocarboxylate transporter 8 (MCT8). By analysing MCT8 deficient mice mutants we demonstrated that MCT8 is crucially involved in mediating the uptake of the active thyroid hormone T3 into the brain. Further analysis will reveal how different neuronal populations will be affected by the absence of this thyroid hormone transporter.

 

in situ hybridization histochemistry

 

 

As shown by in situ hybridization histochemistry, the thyroid hormone transporter MCT8 is highly expressed in hippocampal and neocortical areas of the mouse brain. In contrast to the neuronal expression pattern of MCT8, the enzyme iodothyronine deiodinase type 2 (D2) that converts the prohormone thyroxine to the active compound T3 is mainly found in glia cells.

 

 

  • Role of the TRHergic signaling system in regulating body weight and food intake

Thyrotropin-Releasing Hormone is not only involved in the regulation of the hypothalamus-pituitary thyroid axis but also acts as a neuropeptide in the CNS thereby affecting locomotor activity, autonomic output as well as thermogenesis. In collaboration with Karl Bauer as a guest scientist we aim to define the role of the TRHergic signaling system within the central circuits regulating body weight and food intake by analysing respective mouse mutants.

 

Recent selected publications

  • Trajkovic-Arsic M, Visser TJ, Darras VM, Friesema, ECH, Schlott B, Mittag J, Bauer K, Heuer H (2009) Consequences of MCT8 deficiency for renal transport and metabolism of thyroid hormones in mice. Endocrinology [in press]
  • Horn S, Heuer H (2009) Thyroid hormone action during brain development: More questions than answers. Mol Cell Endocrinol
    [Epub ahead of print]
  • Heuer H, Visser TJ (2009) Minireview: Pathophysiological importance of thyroid hormone transporters. Endocrinology 150(3):1078-83. [PubMed]
  • Mittag J, Friedrichsen S, Strube A, Heuer H, Bauer K (2009) Analysis of Hypertrophic Thyrotrophs in Pituitaries of Athyroid Pax8-/- Mice. Endocrinology. 150, 4443-4449 [PubMed]
  • Hristova M, Cuthill D, Zbarsky V, Acosta-Saltos A, Wallace A, Blight K, Buckley SM, Peebles D, Heuer H, Waddington SN, Raivich G (2009) Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development. Glia. 58, 11-28 [PubMed]
  • Heuer H (2007) The importance of thyroid hormone transporters for brain development and function. Best Pract Res Clin Endocrinol Metab. 21, 265-276. [PubMed]
  • Makwana M, Jones LL, Cuthill D, Heuer H, Bohatschek M, Hristova M, Friedrichsen S, Ormsby I, Bueringer D, Koppius A, Bauer K, Doetschman T, Raivich G (2007) Endogenous transforming growth factor beta 1 suppresses inflammation and promotes survival in adult CNS. J Neurosci. 27, 11201-11213. [PubMed]
  • Trajkovic M, Visser TJ, Mittag J, Horn S, Lukas J, Darras VM, Raivich G, Bauer K, Heuer H (2007) Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. J Clin Invest. 117, 627-635. [PubMed]
  • Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ (2006) Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8. Nat Clin Pract Endocrinol Metab. 2, 512-523. [PubMed]
  • Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, Bauer K (2005) The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations. Endocrinology. 146, 1701-1706. [PubMed]
  • Mittag J, Friedrichsen S, Heuer H, Polsfuss S, Visser TJ, Bauer K (2005) Athyroid Pax8-/-mice cannot be rescued by the inactivation of thyroid hormone receptor alpha1. Endocrinology. 146, 3179-3184. [PubMed]
  • Friedrichsen S, Christ S, Heuer H, Schäfer MK, Mansouri A, Bauer K, Visser TJ (2003) Regulation of iodothyronine deiodinases in the Pax8-/-mouse model of congenital hypothyroidism. Endocrinology. 144, 777-784. [PubMed]
  • Heuer H, Friedrichsen S, Christ S, Winckler M, Brauer D, Bauer K, Raivich G (2003). CTGF as a novel marker of subplate (layerVII) neurons in the rat cerebral cortex. Neurosci. 119, 43-52.
  • Heuer H, Mason CA (2003) Thyroid hormone induces cerebellar Purkinje cell dendritic development via the thyroid hormone receptor alpha1. J Neurosci. 23, 10604-10612. [PubMed]

 

Last update: October 27, 2008
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