A16

A16

Project A16 aims to understand the mechanisms of neurodegeneration during multiple sclerosis (MS), that are not fully understood and insufficiently treated. Consequently, project A16 analyzes cell type-specific mechanisms of neurodegeneration in the MS model experimental autoimmune encephalomyelitis (EAE) in the olfactory bulb, a site that has been long ignored in MS and EAE. Using single nuclei RNA sequencing and immunohistochemistry, project A16 detected a significant infiltration of immune cells of the adaptive and innate immune system in the olfactory bulb. Further, evidence for inflammation-induced changes in expression and/or function of K⁺ channels was obtained by patch-clamp recordings. Project A16 also explored the impact of ATP, ADP and ADO on neurons during CNS inflammation and found, in collaboration with project A04 (Prof. Meier) and project A07 (Prof. Lohr), a contribution of the ATP/ADP receptor P2Y₁ in mitral cell modulation that is driven by neurons and astrocytes expressing this P2 receptor while neuronal ADO A₁ receptors were dispensable for inflammation-induced neurodegeneration. Further, it was discovered in project A16 that mitral cells undergo inflammatory neurodegeneration in experimental autoimmune encephalomyelitis.

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. 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.
2. 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.
3. Rosenkranz SC, Shaposhnykov AA, Träger S, Engler JB, Witte ME, Roth V, Vieira V, Paauw N, Bauer S, Schwencke-Westphal C, Schubert C, Bal LC, Schattling B, Pless O, van Horssen J, Freichel M, Friese MA (2021) Enhancing mitochondrial activity in neurons protects against neurodegeneration in a mouse model of multiple sclerosis. Elife 10:e61798.
4. 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.
5. 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.
6. 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.
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. 
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.