@article{GresleAlexandrouWuetal.2012,
  author    = {Gresle, Melissa M. and Alexandrou, Estella and Wu, Qizhu and Egan, Gary and Jokubaitis, Vilija and Ayers, Margaret and Jonas, Anna and Doherty, William and Friedhuber, Anna and Shaw, Gerry and Sendtner, Michael and Emery, Ben and Kilpatrick, Trevor and Butzkueven, Helmut},
  title     = {Leukemia Inhibitory Factor Protects Axons in Experimental Autoimmune Encephalomyelitis via an Oligodendrocyte-Independent Mechanism},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0047379},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134617},
  pages     = {e47379},
  year      = {2012},
  abstract  = {Leukemia inhibitory factor (LIF) and Ciliary Neurotrophic factor (CNTF) are members of the interleukin-6 family of cytokines, defined by use of the gp130 molecule as an obligate receptor. In the murine experimental autoimmune encephalomyelitis (EAE) model, antagonism of LIF and genetic deletion of CNTF worsen disease. The potential mechanism of action of these cytokines in EAE is complex, as gp130 is expressed by all neural cells, and could involve immuno-modulation, reduction of oligodendrocyte injury, neuronal protection, or a combination of these actions. In this study we aim to investigate whether the beneficial effects of CNTF/LIF signalling in EAE are associated with axonal protection; and whether this requires signalling through oligodendrocytes. We induced MOG\(_{35-55}\) EAE in CNTF, LIF and double knockout mice. On a CNTF null background, LIF knockout was associated with increased EAE severity (EAE grade 2.1\(\pm\)0.14 vs 2.6\(\pm\)0.19; P<0.05). These mice also showed increased axonal damage relative to LIF heterozygous mice, as indicated by decreased optic nerve parallel diffusivity on MRI (1540\(\pm\)207 \(\mu\)m\(^2\)-/s vs 1310\(\pm\)175 \(\mu\)m\(^2\)-/s; P<0.05), and optic nerve (-12.5\%) and spinal cord (-16\%) axon densities; and increased serum neurofilament-H levels (2.5 fold increase). No differences in inflammatory cell numbers or peripheral auto-immune T-cell priming were evident. Oligodendrocyte-targeted gp130 knockout mice showed that disruption of CNTF/LIF signalling in these cells has no effect on acute EAE severity. These studies demonstrate that endogenous CNTF and LIF act centrally to protect axons from acute inflammatory destruction via an oligodendrocyte-independent mechanism.},
  language  = {en}
}
@article{WetzelJablonkaBlum2013,
  author    = {Wetzel, Andrea and Jablonka, Sibylle and Blum, Robert},
  title     = {Cell-autonomous axon growth of young motoneurons is triggered by a voltage-gated sodium channel},
  series = {Channels (Austin)},
  volume    = {7},
  journal   = {Channels (Austin)},
  number    = {1},
  doi       = {10.4161/chan.23153},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132586},
  pages     = {51-56},
  year      = {2013},
  abstract  = {Spontaneous electrical activity preceding synapse formation contributes to the precise regulation of neuronal development. Examining the origins of spontaneous activity revealed roles for neurotransmitters that depolarize neurons and activate ion channels. Recently, we identified a new molecular mechanism underlying fluctuations in spontaneous neuronal excitability. We found that embryonic motoneurons with a genetic loss of the low-threshold sodium channel Na\(_V\)1.9 show fewer fluctuations in intracellular calcium in axonal compartments and growth cones than wild-type littermates. As a consequence, axon growth of Na\(_V\)1.9-deficient motoneurons in cell culture is drastically reduced while dendritic growth and cell survival are not affected. Interestingly, Na\(_V\)1.9 function is observed under conditions that would hardly allow a ligand- or neurotransmitter-dependent depolarization. Thus, Na\(_V\)1.9 may serve as a cell-autonomous trigger for neuronal excitation. In this addendum, we discuss a model for the interplay between cell-autonomous local neuronal activity and local cytoskeleton dynamics in growth cone function.},
  language  = {en}
}
@article{KriegerMetzgerJablonka2014,
  author    = {Krieger, Frank and Metzger, Friedrich and Jablonka, Sibylle},
  title     = {Differentiation defects in primary motoneurons from a SMARD1 mouse model that are insensitive to treatment with low dose PEGylated IGF1},
  series = {Rare Diseases},
  volume    = {2},
  journal   = {Rare Diseases},
  number    = {e29415},
  issn      = {2167-5511},
  doi       = {10.4161/rdis.29415},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120610},
  year      = {2014},
  abstract  = {Muscle atrophy and diaphragmatic palsy are the clinical characteristics of spinal muscular atrophy with respiratory distress type 1 (SMARD1), and are well represented in the neuromuscular degeneration \((Nmd^{2J})\) mouse, modeling the juvenile form of SMARD1. Both in humans and mice mutations in the IGHMBP2 gene lead to motoneuron degeneration. We could previously demonstrate that treatment with a polyethylene glycol-coupled variant of IGF1 (PEG-IGF1) improves motor functions accompanied by reduced fiber degeneration in the gastrocnemius muscle and the diaphragm, but has no beneficial effect on motoneuron survival. These data raised the question which cell autonomous disease mechanisms contribute to dysfunction and loss of Ighmbp2-deficient motoneurons. An analysis of primary Ighmbp2-deficient motoneurons exhibited differentiation deficits such as reduced spontaneous \(Ca^{2+}\) transients and altered axon elongation, which was not compensated by PEG-IGF1. This points to an IGF1 independent mechanism of motoneuron degeneration that deserves treatment approaches in addition to IGF1.},
  language  = {en}
}