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13. GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons

Author

Benamer, N, Marti, F, Lujan, R, Hepp, R, Aubier, T G, Dupin, A. A. M., Frébourg, G, Pons, S, Maskos, Uwe, Faure, P, Hay, Y A, Lambolez, Bertrand, Tricoire, Ludovic, Réseau cortical et couplage neurovasculaire = Cortical Network and Neurovascular (NPS-03), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Castilla-La Mancha (UCLM), Université Pierre et Marie Curie - Paris 6 (UPMC), Neurobiologie intégrative des Systèmes cholinergiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Neurophysiologie et comportements = Neurophysiology and Behavior (NPS-06), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Neurobiologie intégrative des Systèmes cholinergiques (NISC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), HAL-UPMC, Gestionnaire, Neurosciences Paris Seine (NPS), and ANR-16-CE16-0014,SExSy,transmission synaptique lente excitatrice dans les neurones dopaminergiques: role du récepteur au glutamate delta1 (GluD1)(2016)

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Schizophrenia, Delta1 glutamate receptor-channel (GluD1)
Abstract

International audience; Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone. This current is abolished by additional co-expression of a dominant-negative GluD1 dead pore mutant. We then characterized mGlu1-dependent currents in dopamine neurons from midbrain slices. Both the agonist-evoked and the slow postsynaptic currents are abolished by expression of the dominant-negative GluD1 mutant, pointing to the involvement of native GluD1 channels in these currents. Likewise, both mGlu1-dependent currents are suppressed in GRID1 knockout mice, which reportedly display endophenotypes relevant for schizophrenia. It is known that mGlu1 activation triggers the transition from tonic to burst firing of dopamine neurons, which signals salient stimuli and encodes reward prediction. In vivo recordings of dopamine neurons showed that their spontaneous burst firing is abolished in GRID1 knockout mice or upon targeted expression of the dominant-negative GluD1 mutant in wild-type mice. Our results de-orphanize GluD1, unravel its key role in slow glutamatergic transmission and provide insights into how GRID1 gene alterations can lead to dopaminergic dysfunctions in schizophrenia.

Published
2018
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18. Media ethnography for busy people: Introducing students to the ethnographic approach in media-related syllabi

Author

L. Kramp, N. Carpentier, A. Hepp, R. Kilborn, R. Kunelius, H. Nieminen, T. Olsson, P. Pruulmann-Vengerfeldt, I. Tomanić Trivundža, S. Tosoni, Tosoni, Simone, Stiernstedt, Fredrik, Tosoni, Simone (ORCID:0000-0003-4842-0824), L. Kramp, N. Carpentier, A. Hepp, R. Kilborn, R. Kunelius, H. Nieminen, T. Olsson, P. Pruulmann-Vengerfeldt, I. Tomanić Trivundža, S. Tosoni, Tosoni, Simone, Stiernstedt, Fredrik, and Tosoni, Simone (ORCID:0000-0003-4842-0824)

Abstract

Teaching media ethnography

Published
2016

20. Definitive accelerated-hyperfractionated (AHF) Chemoradiotherapy (CRT) vs. neoadjuvant AHF-CRT and Surgery (S) for Patients with operable NSCLC in Stage IIIA(N2)/IIIB after Induction Chemotherapy (IND-C) : Results of a randomized Multicentre Study

Author

Stuschke, Martin, Pöttgen, Christoph, Gauler, Thomas, Friedel, G., Veit, S., Heinrich, V., Gkika, E., Hepp, R., Welter, Stefan, Spengler, W., Schmidberger, H., Lutke-Brintrup, D., Lehmann, Nils, Jöckel, Karl-Heinz, Schuler, Martin, Stamatis, Georgios, and Eberhardt, Wilfried

Subjects
Medizin
Published
2014

25. Phase III study of surgery (S) versus definitive concurrent chemoradiotherapy boost (def ccCRTx-BOx) in patients (pts) with operable (OP+) stage IIIA(N2)/selected IIIb (sel IIIB) non-small cell lung cancer (NSCLC) following induction (IND) chemotherapy (CTx) and concurrent CRTx (ESPATUE)

Author

Eberhardt, Wilfried, Gauler, Thomas, Pöttgen, Christoph, Friedel, G., Veit, S., Heinrich, V., Welter, Stefan, Spengler, W., Kimmich, M., Fischer, B., Schmidberger, H., Gkika, E., Cordes, S., Hepp, R., Luetke-Brintrup, D., Lehmann, Nils, Schuler, Martin, Jöckel, Karl-Heinz, Stamatis, Georgios, Stuschke, Martin, and ESPATUE AIO ARO Clinical Trials

Subjects
Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Medizin, non-small cell lung cancer (NSCLC), medicine.disease, Concurrent chemoradiotherapy, Surgery, Oncology, medicine, In patient, Stage IIIa, business
Abstract

7510 Background: Def ccCRTx or ccCRTx + S are accepted therapies (Tx) for OP+ stage IIIA(N2) NSCLC (Albain 2009). Our multicenter phase-II showed efficacy of CTx + ccCRTx + S in IIIA(N2) / sel IIIB...

Published
2014
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26. βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

Author

Christoph, D C, primary, Kasper, S, additional, Gauler, T C, additional, Loesch, C, additional, Engelhard, M, additional, Theegarten, D, additional, Poettgen, C, additional, Hepp, R, additional, Peglow, A, additional, Loewendick, H, additional, Welter, S, additional, Stamatis, G, additional, Hirsch, F R, additional, Schuler, M, additional, Eberhardt, W E E, additional, and Wohlschlaeger, J, additional

Published
2012
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29. Long-term survival (LTS) and competing risks within a prospective multi center German randomized trial comparing induction chemotherapy (CTx) followed by concurrent (cc) chemoradiation (CTx/RTx) plus surgery (SURG; TRIMODALITY) supplemented by PCI versus local treatment (Tx) alone (SURG + RTx) in operable IIIA NSCLC.

Author

Gauler, T. C., primary, Poettgen, C., additional, Wagner, H., additional, Korfee, S., additional, Hepp, R., additional, Stamatis, G., additional, Von Pawel, J., additional, Passlick, B., additional, Budach, V., additional, Wilke, H., additional, Seeber, S., additional, Stuschke, M., additional, and Eberhardt, W. E. E., additional

Published
2011
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30. Long-term survival (S) of induction chemotherapy (CTx) with three cycles cisplatin (cis)/paclitaxel (pac) followed by concurrent (cc) chemoradiation (CTx/RTx) cis/etoposide (eto) and 45 Gy (1.5 Gy bid) plus surgery (SURG): Phase II results (CISTAXOL).

Author

Eberhardt, W. E. E., primary, Gauler, T. C., additional, Le Pechoux, C., additional, Hepp, R., additional, Welter, S., additional, Fischer, B., additional, Bildat, S., additional, Grunenwald, D., additional, Stamatis, G., additional, Stuschke, M., additional, and Poettgen, C., additional

Published
2011
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42. ARTERIAL HYPERTENSION INDUCED BY 9α-FLUOROCORTISOL IN RATS

Author

Hepp, R., Garbade, K., Oster, P., and Gross, F.

Abstract

In unilaterally nephrectomized rats, 9α-fluorocortisol (9α-FF), in doses of 0.3 and 1.0 mg given daily by intramuscular injection, induced an increase in blood pressure that was independent of additional sodium supply.9α-FF reduced weight gain and, in the dose of 1.0 mg, increased fluid turnover when 0.9 % saline was given to drink. Haematocrit values were elevated, whether saline or water was given as drinking fluid.The serum sodium concentration was increased when saline was offered, but normal with water as drinking fluid. The serum potassium concentration was diminished in all groups that received 9α-FF.The renin content of the kidney was markedly depressed in all groups that had 9α-FF. The degree of suppression was similar in the groups that had saline and those that had water to drink. Under 9α-FF, plasma concentration of angiotensin II was virtually zero when saline was given to drink, but about ¼ to ½ normal when drinking fluid was water.It is concluded that the type of hypertension developing under high doses of 9α-FF resembles glucocorticoid rather than mineralocorticoid hypertension.

Published
1974
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43. The Influence of Tracers on Insulin Binding to Human Erythrocytes

Author

Peters F, Passlack W, Meyer He, Hepp R, and Hans Reinauer

Subjects
Adult, Male, medicine.medical_specialty, Erythrocytes, medicine.medical_treatment, Clinical Biochemistry, education, Biology, Iodine Radioisotopes, Structure-Activity Relationship, Low affinity, Reference Values, Internal medicine, medicine, Receptor model, Humans, Insulin, Receptor, Scatchard plot, Computers, Biochemistry (medical), General Medicine, Receptor, Insulin, Red blood cell, Kinetics, Endocrinology, medicine.anatomical_structure, Human erythrocytes
Abstract

We studied insulin binding to human erythrocytes using two different 125I-insulin-tracers. Erythrocytes of 8 normal subjects were examined using [mono-125II-(Tyr A 14)insulin as tracer. Three of these erythrocyte preparations were examined simultaneously using [125I]insulin, which was randomly iodinated by the chloramine-T-method. Data were analysed by a computerized non-linear least-squares procedure both on the basis of one and two class receptor models. Only the one class receptor model yielded consistent results. When the two class receptor model was applied the low affinity branch of the Scatchard plot was not reproducible. On the basis of the one class receptor model the number of receptor sites was lower (R0 = 0.046 +/- 0.006 nmol/l equivalent to 6.3 +/- 0.8 receptors/erythrocyte) with [mono-125I-(Tyr A 14)]insulin as compared to [125I]insulin randomly iodinated by the chloramine-T method (R0 = 0.070 +/- 0.008 nmol/l equivalent to 9.6 +/- 1.1 receptors/erythrocyte). Conversely, the affinity of the [mono-125I-(Tyr A 14)]insulin was higher (Ka = 2.6 +/- 0.3 x 10(9) l . mol-1 vs. 1.9 +/- 0.2 x 10(9) l . mol-1.

Published
1983

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