A16

A16: Summary

Multiple sclerosis (MS) causes neuroinflammation that result in demyelination, axonal and neuronal degeneration. This project aims to determine the role of ADO receptor A1-dependent neuroprotective signaling pathways for preserving the functional and physical integrity of neurons in experimental autoimmune encephalomyelitis (EAE), the rodent model of MS. By monitoring the electrophysiological and gene expression changes of mitral cells of the olfactory bulb during EAE, we will generate a comprehensive view of the pathophysiological mechanisms that drive inflammation-induced neurodegeneration and explore treatments of neuroinflammation by purinergic neuroprotection.

Dr. Daniela Hirnet

Selected publications

 

  1. Lohr C, Grosche A, Reichenbach A, Hirnet D (2014) Purinergic neuron-glia interactions in sensory systems. Pflugers Arch 466:1859-1872.
  2. Fischer T, Rotermund N, Lohr C, Hirnet D (2012) P2Y1 receptor activation by photolysis of caged ATP enhances neuronal network activity in the developing olfactory bulb. Purinergic Signal 8:191-198.
  3. Thyssen A, Hirnet D*, Wolburg H, Schmalzing G, Deitmer JW, Lohr C (2010) Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling. Proc Natl Acad Sci USA 107:15258-15263. *equal contribution as first authors
  4. Doengi M, Hirnet D, Coulon P, Pape HC, Deitmer JW, Lohr C (2009) GABA uptake-dependent Ca(2+) signaling in developing olfactory bulb astrocytes. Proc Natl Acad Sci USA 106:17570-17575.
  5. De Saint Jan D, Hirnet D, Westbrook GL, Charpak S (2009) External tufted cells drive the output of olfactory bulb glomeruli. J Neurosci 29:2043-2052.
  6. Stumpf T, Zhang Q, Hirnet D, Lewandrowski U, Sickmann A, Wissenbach U, Dörr J, Lohr C, Deitmer JW, Fecher-Trost C (2008) The human TRPV6 channel protein is associated with cyclophilin B in human placenta. J Biol Chem 283:18086-18098.
  7. Becker HM, Hirnet D, Fecher-Trost C, Sültemeyer D, Deitmer JW (2005) Transport activity of MCT1 expressed in Xenopus oocytes is increased by interaction with carbonic anhydrase. J Biol Chem 280:39882-39889.
  8. Erler I, Hirnet D, Wissenbach U, Flockerzi V, Niemeyer BA (2004) Ca2+-selective transient receptor potential V channel architecture and function require a specific ankyrin repeat. J Biol Chem 279:3445634463.
  9. Hirnet D, Olausson J, Fecher-Trost C, Bödding M, Nastainczyk W, Wissenbach U, Flockerzi V, Freichel M (2003) The TRPV6 gene, cDNA and protein. Cell Calcium 33:509-518.
  10. Philipp S, Strauss B, Hirnet D, Wissenbach U, Mery L, Flockerzi V, Hoth M (2003) TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes. J Biol Chem 278:26629-26638.

Prof. Dr. Manuel Alexander Friese

Selected publications

 

  1. Engler JB, Kursawe N, Solano ME, Patas K, Wehrmann S, Heckmann N, Lühder F, Reichardt HM, Arck PC, Gold SM, Friese MA (2017) Glucocorticoid receptor in T cells mediates protection from autoimmunity in pregnancy. Proc Natl Acad Sci USA 114:E181-E190.
  2. Schattling B, Fazeli W, Engeland B, Liu Y, Lerche H, Isbrandt D, Friese MA (2016) Activity of Na(V)1.2 promotes neurodegeneration in an animal model of multiple sclerosis. JCI Insight 1:e89810.
  3. Ufer F, Vargas P, Engler JB, Tintelnot J, Schattling B, Winkler H, Bauer S, Kursawe N, Willing A, Keminer O, Ohana O, Salinas-Riester G, Pless O, Kuhl D, Friese MA (2016) Arc/Arg3.1 governs inflammatory dendritic cell migration from the skin and thereby controls T cell activation. Sci Immunol 1:eaaf8665.
  4. Piédavent-Salomon M*, Willing A*, Engler JB, Steinbach K, Bauer S, Eggert B, Ufer F, Kursawe N, Wehrmann S, Jäger J, Reinhardt S, Friese MA (2015) Multiple sclerosis associated genetic variants of CD226 impair regulatory T cell function. Brain.138:3263-3264. *both authors contributed equally
  5. Willing A, Leach OA, Ufer F, Attfield KE, Steinbach K, Kursawe N, Piedavent M, Friese MA (2014) CD8+ MAIT cells infiltrate into the CNS and alterations in their blood frequencies correlate with IL-18 serum levels in multiple sclerosis. Eur J Immunol 44:3119-3128.
  6. Steinbach K, Piedavent M, Bauer S, Neumann JT, Friese MA (2013) Neutrophils amplify autoimmune central nervous system infiltrates by maturing local APCs. J Immunol 191:4531-4539.
  7. Schattling B, Steinbach K, Thies E, Kruse M, Menigoz A, Ufer F, Flockerzi V, Brück W, Pongs O, Vennekens R, Kneussel M, Freichel M, Merkler D, Friese MA (2012) TRPM4 cation channel mediates axonal and neuronal degeneration in experimental autoimmune encephalomyelitis and multiple sclerosis. Nat Med 1805-1811.
  8. Friese MA, Jakobsen KB, Friis L, Etzensperger R, Craner MJ, McMahon RM, Jensen LT, Huygelen V, Jones EY, Bell JI, Fugger L (2008) Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat Med 11:1227-1235.
  9. Tzartos JS*, Friese MA*, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L (2008) Interleukin17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172:146-155. *both authors contributed equally
  10. Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, Vincent A, Fugger L (2007) Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nat Med 12:1483-1489.

Dr. Daniela Hirnet

Division of Animal Physiology, Institue of Zoology

University of Hamburg

Prof. Dr. Manuel Friese

Institute of Neuroimmunology and Multiple Sclerosis (INIMS)

Center for Molecular Neurobiology Hamburg (ZMNH)

Charlotte Schubert

Institute of Neuroimmunology and Multiple Sclerosis (INIMS)

Center for Molecular Neurobiology Hamburg (ZMNH)

Dr. Kristina Schulz

Division of Animal Physiology, Institue of Zoology

University of Hamburg

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de