EURON and THEME joint PhD meeting

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68 EURON and THEME joint meeting 2011 Characterisation of two N-acetylaspartylglutamate synthetases J. Lodder-Gadaczek, M. Eckhardt, V. Gieselmann Institut für Biochemie und Molekularbiologie, Universitätsklinikum Bonn. N-acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the mammalian brain, present in micromolar to millimolar concentrations. NAAG is synthesized in specific neurons by a synthetase catalyzing a condensation of N-acetylaspartate (NAA) and glutamate. After release from synaptic terminals NAAG can be degraded by glutamate carboxypeptidase II (GCPII) or glutamate carboxypeptidase III (GCPIII). The released products can then be transported to oligodendrocytes and astrocytes. We and others (Collard, 2010) identified the NAAG synthetase-I (NAAGS-I) encoded by a ribosomal modification protein rim-like family member B (Rimklb) gene and the NAAG synthetase-II (NAAGS-II) a structurally related protein encoded by a ribosomal modification protein rim-like family member A (Rimkla) gene. Besides NAAGS-II`s production of NAAG we determined the synthesis of an acetylated tripeptide N-acetylaspartylglutamylglutamate (NAAG 2 ), which is not synthesized by NAAGS-I. Tandem mass spectrometric measurements showed NAAG 2 presence in nanomolar concentrations in the murine nervous system, with the highest concentrations in sciatic nerv, spinal cord and stem brain, which correlate with the expression levels of NAAGS-II. The NAAGS-II knock-out mice showed no NAAG 2 . Furthermore we found proof that NAAG and NAAG 2 react in the same metabolic system. This is the first description of the presence of NAAG 2 in the vertebrate nervous system. For now the physiological roles of NAAG 2 are not understood and remain to be determined.
69 EURON and THEME joint meeting 2011 Local overexpression of Interleukin -11 in the central nervous system prevents demyelination A. Maheshwari 1 , H. Slaets 1 , C. Van den Haute 2 , V. Baekelandt 2 , P. Stinissen 1 , J. Hendriks 1 , N. Hellings 1 1 Hasselt University, Biomedical Research Institute,and transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium; 2 Katholieke Universiteit Leuven, Laboratory for Neurobiology and Gene Therapy, Division of Molecular Medicine, Leuven, Belgium. Background & Aim Demyelination is one of the clinical hallmarks of multiple sclerosis (MS). Till today no therapy is available which potentiates the endogenous remyelination. Interleukin-11 (IL-11) is a member of the gp130 family cytokines, that also includes leukemia inhibitory factor and oncostatin M. These neuropoietic cytokines are upregulated in MS lesions and several have been shown to control neuroinflammation. Recently, IL-11 was identified to directly provide trophic support to oligodendrocytes by potentiating their survival and maturation in vitro. Moreover, IL-11 was shown to improve clinical severity in the EAE model. In this study we aim to elucidate the direct in vivo effect of IL-11 demyelination independent of the immune response. Methods To achieve immune independent demyelination, a cuprizone induced demyelination mouse model was used. 0.2% of cuprizone was mixed with powdered chow and fed to 8 week old mice for 5 weeks to achieve acute demyelination. To allow spontaneous remyelination, mice were returned to normal diet after 5 weeks. CNS directed overexpression of IL-11 was achieved by stereotactical administration of IL-11 encoding lentiviral vectors in the striatum of mouse brain. For the prophylactic study, vectors were administered 2 weeks prior to the start of the cuprizone diet and acute demyelination was studied. For the therapeutic study, the vectors were administered 4 weeks after the start of the cuprizone diet. Mice were allowed to remyelinate for 2 weeks and subsequently sacrificed for immunohistochemical analyses (Luxol Fast Blue, Iba-1, NG-2). To study the in vitro effect of IL-11 on myelin phagocytosis, RAW264.7 cells were cultured and treated with 1, 3, 10, 30 and 100 ng/ml of murine rIL-11 for a period of 6 and 12 hrs. The uptake of DI labeled myelin was analysed by flowcytometry. Results Overexpression of IL-11 in mouse brain striatum significantly limited the area of acute demyelination (decrease of 27% as compared to controls) in the
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EURON and THEME joint PhD meeting U
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The local organizing committee: Pro
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Information about THEME 3 EURON and
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5 EURON and THEME joint meeting 201
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EURON a short introduction 7 EURON
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Programme 13 EURON and THEME joint
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Thursday September 22 nd 9:00 - 10:
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Page 25 and 26: EURON Lecture Frank Kirchhoff ADDRE
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Page 29 and 30: THEME Lecture Eckhard Mandelkow POS
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Page 105 and 106: List of Participants 103 EURON and
Page 107 and 108: Nuersailike Abuduwali University of
Page 109 and 110: Marianne Eisenhardt University of B
Page 111 and 112: Sabine Klein University of Bonn PhD
Page 113 and 114: Viktoriya Peeva University of Bonn
Page 115: Sylvie van der Kruijs Maastricht Un
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EURON and THEME joint PhD meeting

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