@article{defa1fe6fb4942c7ae1c563158a07465,
title = "Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple Sclerosis",
abstract = "Axon loss determines persistent disability in multiple sclerosis patients. Here, we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. We rule out the endoplasmic reticulum, glutamate excitotoxicity, and the reversal of the sodium-calcium exchanger as sources of intra-axonal calcium accumulation and instead identify nanoscale ruptures of the axonal plasma membrane as the critical path of calcium entry. Witte et al. identify cytoplasmic calcium accumulations as a key driver of axon degeneration in a model of multiple sclerosis. Calcium accumulates in the axoplasm because nanoscale ruptures of the axonal plasma membrane provide an entry path for extracellular calcium.",
keywords = "axon degeneration, calcium imaging, experimental autoimmune encephalomyelitis, in vivo microscopy, multiple sclerosis, plasma membrane",
author = "Witte, {Maarten E.} and Schumacher, {Adrian Minh} and Mahler, {Christoph F.} and Bewersdorf, {Jan P.} and Jonas Lehmitz and Alexander Scheiter and Paula S{\'a}nchez and Williams, {Philip R.} and Oliver Griesbeck and Ronald Naumann and Thomas Misgeld and Martin Kerschensteiner",
note = "Funding Information: We would like to thank A. Schmalz, L. Sch{\"o}del, B. Fiedler, and Y. Hufnagel for excellent technical assistance and D. Matzek, B. Stahr, and N. and M. Budak for animal husbandry. Work in M.K.{\textquoteright}s laboratory is financed through grants from the DFG ( TRR128 , Project B10 and B13 ), the European Research Council (ERC, FP/2007-2013 ; ERC Grant Agreement no. 310932 ), the BMBF (KKNMS), the DMSG , and the “Verein Therapieforschung f{\"u}r MS-Kranke e.V.” Work in T.M.{\textquoteright}s lab is supported by the DFG ( CIPSM EXC114 , CRC870 , Mi 694/8-1 ) and the ERC ( FP/2007-2013 ; ERC Grant Agreement no. 616791 ). M.K. and T.M. are further supported by the DFG ( Ke 774/5-1/Mi 694/7-1 ) and the Munich Cluster for Systems Neurology (SyNergy; EXC 1010 ). A.S. and J.L. were supported by the Graduate School of the TU M{\"u}nchen ; A.-M.S., C.F.M., and J.P.B. were supported by the “F{\"o}FoLe” program at LMU Munich . P.R.W. was supported by the “Wings for Life” foundation. Funding Information: We would like to thank A. Schmalz, L. Sch{\"o}del, B. Fiedler, and Y. Hufnagel for excellent technical assistance and D. Matzek, B. Stahr, and N. and M. Budak for animal husbandry. Work in M.K.'s laboratory is financed through grants from the DFG (TRR128, Project B10 and B13), the European Research Council (ERC, FP/2007-2013; ERC Grant Agreement no. 310932), the BMBF (KKNMS), the DMSG, and the “Verein Therapieforschung f{\"u}r MS-Kranke e.V.” Work in T.M.'s lab is supported by the DFG (CIPSM EXC114, CRC870, Mi 694/8-1) and the ERC (FP/2007-2013; ERC Grant Agreement no. 616791). M.K. and T.M. are further supported by the DFG (Ke 774/5-1/Mi 694/7-1) and the Munich Cluster for Systems Neurology (SyNergy; EXC 1010). A.S. and J.L. were supported by the Graduate School of the TU M{\"u}nchen; A.-M.S., C.F.M., and J.P.B. were supported by the “F{\"o}FoLe” program at LMU Munich. P.R.W. was supported by the “Wings for Life” foundation. Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2019",
month = feb,
day = "20",
doi = "10.1016/j.neuron.2018.12.023",
language = "English",
volume = "101",
pages = "615--624.e5",
journal = "Neuron",
issn = "0896-6273",
number = "4",
}