P9	Role of glial Ca2+ signals during neuroinflammation, axonal degeneration, and de- and remyelination in the mouse spinal cord

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Project 9 aims to unravel glial calcium signals during the processes of neuroinflammation, axonal degeneration and de/remyelination in spinal cord white matter, these events being prominent neuropathological features in MS.

To achieve this, an array of established reporter mice of both calcium signalling and glial morphology will be visualised by in vivo 2P-LSM. Through the use of two MS animal models, EAE and toxic- cuprizone-evoked demyelination, the glial responses during these processes will be analysed.

These findings will be compared to those in a model of opticospinal experimental autoimmune encephalomyelitis provided by project 1 (Diem/Flockerzi; Neurology Heidelberg/Pharmacology Homburg) and project 4 (Winkler/Williams; Neurology Heidelberg). Project 9 offers a comprehensive spectrum of transgenic mice with cell type-specific expression of fluorescent proteins in the cytoplasm as well as inducible and cell type-specific Cre/loxP system to manipulate calcium channel expression to the consortium. Additional interactions are planned with project 6 (Niemeyer/Alansary; Biophysics Homburg) on T cell characterisation in spinal cord lesions and the mechanisms of T cell invasion and with project 8 (Platten/Meuth; Neurology Heidelberg/Neurology Münster) on imaging of the BBB.

PrincipalInvestigators

Publications

Huang W, Zhao N, Bai X, Karram K, Trotter J, Goebbels S, Scheller A, Kirchhoff F (2014) Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2 glia during development. Glia 62:896-913

Saab AS, Neumeyer A, Jahn HM, Cupido A, Šimek AA, Boele HJ, Scheller A, Le Meur K, Götz M, Monyer H, Sprengel R, Rubio ME, Deitmer JW, De Zeeuw CI, Kirchhoff F (2012) Bergmann glial AMPA receptors are required for fine motor coordination. Science 337:749-53

Ertürk A, Mauch CP, Hellal F, Förstner F, Keck T, Becker K, Jährling N, Steffens H, Richter M, Hübener M, Kramer E, Kirchhoff F, Dodt HU, and Bradke F (2012) Three-dimensional imaging of the unsectioned adult spinal cord to assess axon regeneration and glial responses after injury. Nat Med 18: 166-171

Dibaj P, Nadrigny F, Steffens H, Scheller A, Hirrlinger J, Schomburg ED, Neusch C, Kirchhoff F (2010) NO mediates microglial response to acute spinal cord injury under ATP control in vivo. Glia 58:1133-44

Hirrlinger J, Scheller A, Hirrlinger PG, Kellert B, Tang W, Wehr MC, Goebbels S, Reichenbach A, Sprengel R, Rossner MJ, Kirchhoff F (2009) Split-cre complementation indicates coincident activity of different genes in vivo. PLoS One 4:e4286

Hirrlinger PG, Scheller A, Braun C, Hirrlinger J, Kirchhoff F (2006) Temporal control of gene recombination in astrocytes by transgenic expression of the tamoxifen-inducible DNA recombinase variant CreERT2. Glia 54:11-20

Hirrlinger PG, Scheller A, Braun C, Quintela-Schneider M, Fuss B, Hirrlinger J, Kirchhoff F (2005) Expression of reef coral fluorescent proteins in the central nervous system of transgenic mice. Mol Cell Neurosci 30:291-303

Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314-18

Hirrlinger J, Hülsmann S, Kirchhoff F (2004) Astroglial processes show spontaneous motility at active synaptic terminals in situ. Eur J Neurosci 20:2235-2239

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Role of glial Ca2+ signals during neuroinflammation, axonal degeneration, and de- and remyelination in the mouse spinal cord

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Prof. Dr.

Frank Kirchhoff