A16

A16

Multiple sclerosis (MS) is the most frequent inflammatory disease of the central nervous system (CNS) also resulting in olfactory deficits. However, underlying mechanisms are not understood. The adenine nucleotide axis has a crucial role in regulation of neuro-glia communication and inflammation and thereby qualifies as an attractive switchboard for both. Using the EAE inflammation model we aim to profile the cellular vulnerability and molecular determinants of neurodegeneration in the olfactory bulb and to elucidate the role of the P2Y1R and related P2 receptors in astrocyte-neuron interaction under homeostatic and inflammatory conditions and test their neuroprotective therapeutic potential.

Dr. Daniela Hirnet

Selected publications (*equal contribution)

 

1. Rotermund N, Winandy S, Fischer T, Schulz K, Fregin T, Alstedt N, Buchta M, Bartels J, Carlström M, Lohr C, Hirnet D (2018) Adenosine A1 receptor activates background potassium channels and modulates information processing in olfactory bulb mitral cells. J Physiol 596(4):717-733.
2. Schulz K, Rotermund N, Grzelka K, Benz J, Lohr C, Hirnet D (2018) Adenosine A1 Receptor-Mediated Attenuation of Reciprocal Dendro-Dendritic Inhibition in the Mouse Olfactory Bulb. Front Cell Neurosci 11:435.
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 USA107:15258-15263. *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 (*equal contribution)

 

1. Winkler I, Engler JB, Vieira V, Bauer S, Liu YH, Di Liberto G, Grochowska KM, Wagner I, Bier J, Bal LC, Rothammer N, Meurs N, Egervari K, Schattling B, Salinas G, Kreutz MR, Huang YS, Pless O, Merkler D, Friese MA (2023) MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration. Sci Adv.;9(47):eadi6855.
2. Rothammer N, Woo MS, Bauer S, Binkle-Ladisch L, Di Liberto G, Egervari K, Wagner I, Haferkamp U, Pless O, Merkler D, Engler JB, Friese MA (2022) G9a dictates neuronal vulnerability to inflammatory stress via transcriptional control of ferroptosis. Sci Adv. 8(31):eabm5500.
3. Woo MS, Ufer F, Rothammer N, Di Liberto G, Binkle L, Haferkamp U, Sonner JK, Engler JB, Hornig S, Bauer S, Wagner I, Egervari K, Raber J, Duvoisin RM, Pless O, Merkler D, Friese MA (2021) Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation. J Exp Med 3;218(5):e20201290.
4. Kaufmann M, Evans H, Schaupp AL, Engler JB, Kaur G, Willing A, Kursawe N, Schubert C, Attfield KE, Fugger L, Friese MA (2021) Identifying CNS-colonizing T cells as potential therapeutic targets to prevent progression of multiple sclerosis. Med 12;2(3):296-312.e8.
5. Schattling B, Engler JB, Volkmann C, Rothammer N, Woo MS, Petersen M, Winkler I, Kaufmann M, Rosenkranz SC, Fejtova A, Thomas U, Bose A, Bauer S, Träger S, Miller KK, Brück W, Duncan KE, Salinas G, Soba P, Gundelfinger ED, Merkler D, Friese MA (2019) Bassoon proteinopathy drives neurodegeneration in multiple sclerosis. Nat Neurosci 22(6):887-896.
6. 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.
7. 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.
8. 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.
9. 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.
10. Friese MA, Craner MJ, Etzensperger R, Vergo S, Wemmie JA, Welsh MJ, Vincent A, Fugger (2007) L. Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system. Nature Med 1483-1489.