Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Regulation of glutamate transporters in neurodegenerative diseases
Topics Research team Equipment Techniques Recent publications Collaborations	Primary cultured astrocytes(GFAP/DAPI staining)

[UCL][Faculties][Faculty of Medicine]

last update : April 19^th, 2007 – contacts  : Emmanuel Hermans 

Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Regulation of glutamate transporters in neurodegenerative diseases

Topics

For several years, our research has concerned the homologous regulation of a variety of membrane receptor to neurotransmitters (muscarinic receptors, benzodiazepine receptor, neurotensin receptor, dopamine receptors …).

Since 2001, we have focused our attention on the regulation of glutamate transporters, in particular their modulation by intracellular signallings which are activated by membrane receptors.

The amino acid glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. The simplicity of the chemical structure of this transmitter contrasts with the complexity of biological molecules involved in its specific recognition and uptake. More than 4 families of cell surface receptors and 5 subtypes of specific transporters have been identified. In response to physiological and pharmacological stimuli, the expression, the subcellular localisation and the activity of these proteins are timely controlled.

Glutamate is not metabolised within the extracellular space, and its clearance is highly dependent on the activity of high affinity, specific glutamate transporters which are principally localised on glial cells. For this reason, astrocytes play a critical role in the protection of neuronal cells against the potential toxicity of excessive glutamate concentrations.

Heterologous regulation of glutamate transporters in cultured astrocytes and glioma cells (Stéphanie Goursaud and Marylène Focant)

Characterization of glutamate uptake and growth factor release in astrocytic cells derived from neural stem cells and mesenchymal stem cells (Cédric Boucherie)

Pharmacological modulation of glutamate transporters in neuro-inflammatory conditions, crosstalk between astrocytes and microglial cells (Sebastien Tilleux)

Alteration of glutamate transporter in glioma cells and involvement in tumour growth (Nicolas Vanhoutte)

Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Regulation of glutamate transporters in neurodegenerative diseases

Research team

The team is headed by Pr. Emmanuel Hermans, who has been working in the field of neuropharmacology for more than 12 years. After his PhD in Pharmaceutical Sciences (in neurochemistry), he spent six months in Paris (Laboratory of neuroendocrinology, Pr W. Rostène) and two years in Leicester, UK (Dpt of Cell Physiology and Pharmacology, Pr S.R. Nahorski). Since 1998, Emmanuel Hermans is permanent researcher and associate professor in the laboratory.

Currently (uptaded April 2007), the team is composed of 6 PhD students or Post-docs.

Stéphanie Goursaud (Post-doc)

Sébastien Tilleux (4^th year PhD in Pharmaceutical Sciences)

Nicolas Vanhoutte (3^nd year PhD in Biomedical Sciences)

Cédric Boucherie (3^nd year PhD in Biomedical Sciences)

Marylène Focant (1st year PhD in Biomedical Sciences)

Bery Koener (will start a PhD in Biomedical Sciences in Sept 2007)

Julie Berger (will start a PhD Pharmaceutical Sciences in Sept 2007)

Anne Lebbe (Technician)

Hendrik Lenaert (Technician)

Thérèse Timmerman (Technician)

Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Regulation of glutamate transporters in neurodegenerative diseases

Equipment

· Cell culture facilities

· Fluorescence inverted microscope

· Cryostat and material fro in situ hybridisation and immunocytochemistry

· Paw thermal stimulator

· Conventional equipement for molecular biology

· Real Time PCR (BioRad)

· Paw thermal stimulator

· Protein electrophoresis

· Brandel Harvester (for radioligand binding assays)

· Rat stereotaxic frame

· Scintillation counters

· Ultracentrifuges

· Local animal housing facility (rodents)

· Image analysis station (MCID and Till photonics)

Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Regulation of glutamate transporters in neurodegenerative diseases

Techniques

· Cell culture (primary cultures of astrocytes, neurones, mesenchymal stem cells, neural stem cells)

· Radioligand binding assays

· Second messenger assays (intracellular calcium, inositol phosphates)

· Protein biochemistry (Western blot, immunoprecipitation)

· Autoradiography

· Image analysis

· Molecular biology (cloning, RT-PCR, Real-time PCR, transfection, Northern blot,…)

· Immunocytochemistry and immunohistochemistry

· In situ hybridisation

· Stereotaxic injections in the CNS

· Pain evaluation

Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Regulation of glutamate transporters in neurodegenerative diseases

Recent publications

Bosier B., Hermans E. (2007)

Versatility of GPCR recognition by drugs, from biological implications to therapeutic relevance

Trends in Pharmacol. Sci. under revision

Tilleux S., Hermans E. (2007)

Neuroinflammation and the regulation of glial glutamate uptake in neurological disorders.

J. Neurosci. Res. In press

Bosier B., Tilleux S., Najimi M., Lambert D.M., Hermans E. (2007)

Agonist selective modulation of tyrosine hydroxylase expression by cannabinoid ligands in a murine neuroblastoma cell line.

J. Neurochem. in press

de Hemptinne I., Boucherie C., Pochet R., Bantubungi K., Schiffmann S.N., Maloteaux J.M., Hermans E. (2006)

Unilateral induction of progenitors in the spinal cord of hSOD1(G93A) transgenic rats correlates with an asymmetrical hind limb paralysis.

Neurosci Lett. 401, 25-9

Caumont A.S., Octave J.N., Hermans E. (2006)

Specific regulation of rat glial cell line-derived neurotrophic factor gene expression by riluzole in C6 glioma cells.

J. Neurochem. 97, 128-139

Vermeiren C., de Hemptinne I., Vanhoutte, N., Tilleux, S., Maloteaux J.M., Hermans E. (2006)

Loss of metabotropic glutamate receptor-mediated regulation of glutamate transport in chemically activated astrocytes in a rat model of amyotrophic lateral sclerosis.

J. Neurochem. 96, 719-731

Caumont A.S., Octave J.N., Hermans E. (2006) Amantadine and memantine induce the expression of the glial cell line-derived neurotrophic factor in C6 glioma cells.

Neurosci Lett. 394, 196-201

Vermeiren C., Najimi N., Vanhoutte, N., Tilleux, S., de Hemptinne I., Maloteaux J.M., Hermans E. (2005)

Acute upregulation of glutamate uptake mediated by mGluR5 in reactive astrocytes.

J. Neurochem. 94, 405-16

Najimi N., Maloteaux J.M., Hermans E. (2005)

Pertussis toxin-sensitive modulation of glutamate transport by endothelin-1 type A receptors in glioma cells

Biochim. Biophys. Acta Biomembranes 1668, 195-202.

Vermeiren C., Najimi N., Maloteaux J.M., Hermans E. (2005)

Molecular and functional characterisation of glutamate transporters in rat cortical astrocytes exposed to a defined combination of growth factors during in vitro differentiation.

Neurochem. Int. 46, 137-147.

Vanhoutte N., de Hemptinne I., Vermeiren C., Maloteaux J.M., Hermans E. (2004)

In vitro differentiated neural stem cells express functional glial glutamate transporters.

Neurosci. Lett. 370, 230-237.

de Hemptinne I., Vermeiren C., Maloteaux J.M., Hermans E. (2004)

Induction of glial glutamate transporters in adult
mesenchymal stem cells.

J. Neurochem. 91, 155-166

Hermans E. (2004)

Generation of Model Cell Lines Expressing Recombinant G-Protein-Coupled Receptors.

Receptor Signal Transduction Protocols 259, 137-154 (Humana Press - ISBN 1-58829-329-7) [abstract]

Peeters M., Romieu P., Maurice T., Su T.P., Maloteaux J.M., Hermans E. (2004)
Involvement of the sigma1 receptor in the modulation of dopaminergic transmission by amantadine.
Eur. J. Neurosci. 19, 2212-2220 [abstract]

Geurts M., Maloteaux J.M., Hermans E. (2003)
Altered expression of regulators of G-protein signaling (RGS) RNAs in the striatum of rats undergoing dopamine depletion. 
Biochem. Pharmacol. 166, 1163-1170 [abstract]

Skrzydelski D., Lhiaubet A.M., Lebeau A., Forgez P., Yamada M., Hermans E., William Rostene W., Pelaprat D. (2003)
Differential involvement of intracellular domains of the rat NST1 neurotensin receptor in coupling to G proteins.
Mol. Pharmacol. 64, 421-429 [abstract]

Hermans E. (2003)
Biochemical and pharmacological control of the multiplicity of coupling at G protein coupled receptors.
Pharmacol. Therap. 99, 25-44 [abstract]

Peeters M., Maloteaux J.M., Hermans E. (2003)
Distinct effects of amantadine and memantine on dopaminergic transmission in the rat striatum.
Neurosci. Lett. 343, 205-209 [abstract]

Geurts M., Hermans E., Maloteaux J.M. (2002)
Opposite modulation of regulators of G protein signalling-2 RGS2 and RGS4 expression by dopamine receptors in the rat striatum.
Neurosci Lett. 333, 146-50 [abstract]

Page, G., Chalon, S., Emond, P., Maloteaux, J-M. and Hermans, E. (2002)
Pharmacological characterisation of (E)-N-(3-iodoprop-2-enyl)-2-carbomethoxy-3beta-(4’-methylphenyl) nortropane (PE2I) binding to the rat neuronal dopamine transporter expressed in COS cells.
Neurochem. Int. 40, 105-113  [abstract]

Peeters, M., Page, G., Maloteaux, J-M. and Hermans E. (2002)
Hypersensitivity of dopamine transmission in the rat striatum after treatment with NMDA receptor antagonist amantadine.
Brain Res. 949, 32-41[abstract]

Najimi, M., Gailly, P., Maloteaux, J-M. and Hermans, E. (2002)
Distinct regions of C-terminus of the high affinity neurotensin receptor mediate the functional coupling with pertussis toxin sensitive and insensitive G-proteins.
FEBS Lett. 512, 329-333 [abstract]

Najimi, M., Maloteaux, J-M. and Hermans, E. (2002)
Cytoskeleton-related trafficking of the EAAC1 glutamate transporter after activation of the Gq/11-coupled neurotensin receptor NTS1.
FEBS Lett. 523, 224-228  [abstract]

Grisshammer, R. and Hermans, E. (2001)
Functional coupling with Galpha(q) and Galpha(i1) protein subunits promotes high-affinity agonist binding to the neurotensin receptor NTS-1 expressed in Escherichia coli.
FEBS Lett. 493, 101-105 [abstract]

Hermans, E. and Challiss R.A.J.(2001)
Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G protein-coupled receptors.
Biochem. J. 359, 465-484 [abstract]

Najimi, M., Hermans, E., Rostène, W. and Forgez, P. (2001)
Transcriptional regulation of the tyrosine hydroxylase gene by neurotensin in human neuroblastoma CHP 212 cells.
Metab. Brain Dis.16, 165-174 [abstract]

Page, G., Peeters, M., Najimi, M., Maloteaux, J.M. and Hermans, E. (2001)
Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes.
J. Neurochem. 76, 1282-1290 [abstract]

Robinet, E.A, Geurts, M., Maloteaux, J.M. and Pauwels, P.J. (2001)
Chronic treatment with certain antipsychotic drugs preserves upregulation of regulator of G-protein signalling 2 RNA in rat striatum as opposed to c-fos mRNA.
Neurosci. Lett. 307, 45-48 [abstract]

Gailly, P., Najimi, M. and Hermans, E. (2000)
Evidence for the dual coupling of the rat neurotensin receptor with pertussis toxin-sensitive and insensitive G-proteins.
FEBS Lett. 483, 109-113 [abstract]

Page, G., Peeters, M., Maloteaux, J.M. and Hermans, E. (2000)
Increased dopamine uptake in striatal synaptosomes after treatment of rats with amantadine.
Eur. J. Pharmacol. 403, 75-80 [abstract]

Neuropharmacology group Emmanuel Hermans Jean-Marie Maloteaux Molecular and cellular mechanisms of the regulation of glutamate transporters

Collaborations

Dr Thierry Gustin (Mont Godinne, Belgium)

Pr Roland Pochet (Brussels, Belgium)

Pr Didier Lambert (Brussels, Belgium)

Dr Guylène Page (Poitiers, France)

Dr Tangui Maurice (Montpellier, France)

Pr Bernard Rogister (Liège, Belgium)

Dr Didier Pelaprat (Paris, France)

Dr Christian Damblon (Leicester, United Kingdom)

Pr Philippe Gailly (Brussels, Belgium)

Dr Mustapha Najimi (Brussels, Belgium)

Prs Marc de Kock & Patricia Lavand’homme (Brussels, Belgium)