The adult vertebrate central nervous system (CNS) mainly consists of neurons, astrocytes, microglia cells and oligodendrocytes. Oligodendrocytes, the myelin-forming cells of the CNS, are subjected to cell stress and subsequent death in a number of metabolic or inflammatory disorders, among which is multiple sclerosis (MS). This disease is associated with the development of large demyelinated plaques, oligodendrocyte destruction and axonal degeneration, paralleled by the activation of astrocytes and microglia as well as the recruitment of peripheral immune cells to the site of tissue injury. Of note, viable oligodendrocytes and an intact myelin sheath are indispensable for neuronal health. For example, it has been shown that oligodendrocytes provide nutritional support to neurons, that fast axonal transport depends on proper oligodendrocyte function, and that mice deficient in mature myelin proteins eventually display severe neurodegeneration.

Our group is interested to understand the physiology and pathology of the axon-oligodendrocyte-myelin unit. Particularly, we are interested to understand to what extend stressed oligodendrocytes regulate peripheral immune cell recruitment, and by which neuroanatomical pathways peripheral immune cells gain access into the CNS parenchyma. To address our scientific challenges we use state of the art techniques such as design-based stereology, a set of behavioral analyses such as high speed ventral plane videography, or positron emission tomography/computed tomography. Whenever possible, we compare our pre-clinical results with post-mortem samples, obtained from MS patient donors.

Another focus of our group is the usability of wearable sensors to follow the physical and mental health of multiple sclerosis patients. The central aim of this project is to provide a proof of concept that multiple physical and cognitive parameters can be monitored in real-time by wearable medical sensors and mobile application software tools (i.e.; apps), and can be integrated as outcome parameters into clinical trials.

• Clarner, Tim; Department of Neuroanatomy, RWTH Aachen University, Germany
• Schmitz, Christoph; Department of Neuroanatomy, Ludwig-Maximilians-University, München, Germany
• Amor, Sandra; Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands
• Morrison, Helen; Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany
• Spindler, Volker; Department of Biomedicine, University of Basel, Basel, Switzerland
• Calegari, Federico; CRTD - Center for Regenerative Therapies Dresden, School of Medicine, TU Dresden, Dresden, Germany
• Krause, Bernd Joachim; Department of Nuclear Medicine, University Medicine Rostock, Rostock, Germany
• Ponsaerts, Peter; Laboratory of Experimental Hematology, University of Antwerp, Belgium
• Denecke, Bernd; Interdisciplinary Centre for Clinical Research (IZKF) Aachen, Uniklinik RWTH Aachen, Germany

Licht-Mayer S, Campbell GR, Canizares M, Mehta AR, Gane AB, McGill K, Ghosh A, Fullerton A, Menezes N, Dean J, Dunham J, Al-Azki S, Pryce G, Zandee S, Zhao C, Kipp M, Smith KJ, Baker D, Altmann D, Anderton SM, Kap YS, Laman JD, Hart BA', Rodriguez M, Watzlawick R, Schwab JM, Carter R, Morton N, Zagnoni M, Franklin RJM, Mitchell R, Fleetwood-Walker S, Lyons DA, Chandran S, Lassmann H, Trapp BD, Mahad DJ. (2020) Enhanced axonal response of mitochondria to demyelination offers neuroprotection: implications for multiple sclerosis. Acta Neuropathol. 2020 Aug;140(2):143-167

Fischbach F, Nedelcu J, Leopold P, Zhan J, Clarner T, Nellessen L, Beißel C, van Heuvel Y, Goswami A, Weis J, Denecke B, Schmitz C, Hochstrasser T, Nyamoya S, Victor M, Beyer C, Kipp M (2019) Cuprizone-induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damage-inducible transcript 3. Glia. 2019 Feb;67(2):263-276

Rüther BJ, Scheld M, Dreymueller D, Clarner T, Kress E, Brandenburg LO, Swartenbroekx T, Hoornaert C, Ponsaerts P, Fallier-Becker P, Beyer C, Rohr SO, Schmitz Ch, Chrzanowski U, Hochstrasser T, Nyamoya S, and Kipp M (2017) Combination of cuprizone and experimental autoimmune encephalo-myelitis to study inflammatory brain lesion formation and progression. Glia 2017 Dec;65(12):1900-1913

Clarner T, Diederichs F, Berger K, Denecke B, Gan L, van der Valk P, Beyer C, Amor S, Kipp M (2012) Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions. Glia.60(10):1468-80.

Clarner T, Janssen K, Nellessen L, Stangel M, Skripuletz T, Krauspe B, Hess FM, Denecke B, Beutner C, Linnartz-Gerlach B, Neumann H, Vallieres L, Amor S, Ohl K, Tenbrock K, Beyer C, Kipp M (2015) CXCL10 triggers early microglial activation in the cuprizone model. Journal of immunology.194(7):3400-13.

Huizinga R, van der Star BJ, Kipp M, Jong R, Gerritsen W, Clarner T, Puentes F, Dijkstra CD, van der Valk P, Amor S (2012) Phagocytosis of neuronal debris by microglia is associated with neuronal damage in multiple sclerosis. Glia.60(3):422-31.

Janssen K, Rickert M, Clarner T, Beyer C, Kipp M (2016) Absence of CCL2 and CCL3 Ameliorates Central Nervous System Grey Matter But Not White Matter Demyelination in the Presence of an Intact Blood-Brain Barrier. Molecular neurobiology.53(3):1551-64.

Kipp M, Gingele S, Pott F, Clarner T, van der Valk P, Denecke B, Gan L, Siffrin V, Zipp F, Dreher W, Baumgartner W, Pfeifenbring S, Godbout R, Amor S, Beyer C (2011) BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions. Brain, behavior, and immunity.25(8):1554-68.

Scheld M, Ruther BJ, Grosse-Veldmann R, Ohl K, Tenbrock K, Dreymuller D, Fallier-Becker P, Zendedel A, Beyer C, Clarner T, Kipp M (2016) Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain. The Journal of neuroscience : the official journal of the Society for Neuroscience.36(4):1410-5.

Skripuletz T, Hackstette D, Bauer K, Gudi V, Pul R, Voss E, Berger K, Kipp M, Baumgartner W, Stangel M (2013) Astrocytes regulate myelin clearance through recruitment of microglia during cuprizone-induced demyelination. Brain: a journal of Neurology.136(Pt 1):147-67.

DFG (Markus Kipp): Aktivierung der "unfolded Protein Response" bei Multipler Sklerose: Funktion im Rahmen der Läsionsentstehung und Progression

Novartis-Pharma (Markus Kipp): Mode of action of protective Siponimod effects during toxic demyelination

FORUN-Programm UMR (Teresa Alberts): Kleintier-PET/CT-Analysen mit dem TSPO Tracer [18F]GE-180 zur Quantifizierung der Gliaaktivierung in Mausmodellen neurodegenerativer Erkrankungen

FORUN-Programm UMR (Katerina Gerdinand): Kontinuierliches Monitoring von physiologischen und kognitiven Parametern bei MS-Patienten mit Hilfe von tragbaren Sensoren und Softwaretools für mobile Anwendungen in Rahmen von klinischen Studien

Novartis-Pharma (Markus Kipp): WeSeniMuS (Wearable Sensors in Multiple Sclerosis)

Ministry of Education, P.R. China (Jiangshan Zhan): China Scholarship Council (CSC) Scholarship

DAAD (Newshan Behrangi): Research Grants-Doctoral Programme in Germany