@article{FereroRiveroWaeldchenetal.2017,
  author    = {Ferero, Andrea and Rivero, Olga and W{\"a}ldchen, Sina and Ku, Hsing-Ping and Kiser, Dominik P. and G{\"a}rtner, Yvonne and Pennington, Laura S. and Waider, Jonas and Gaspar, Patricia and Jansch, Charline and Edenhofer, Frank and Resink, Th{\´e}r{\`e}se J. and Blum, Robert and Sauer, Markus and Lesch, Klaus-Peter},
  title     = {Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {11},
  journal   = {Frontiers in Cellular Neuroscience},
  number    = {307},
  doi       = {10.3389/fncel.2017.00307},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170313},
  year      = {2017},
  abstract  = {Background: During early prenatal stages of brain development, serotonin (5-HT)-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR), innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13) has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system. Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency. Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs), which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5. Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell density of the developing DR and the posterior innervation of the prefrontal cortex (PFC), and therefore might be involved in the migration, axonal outgrowth and terminal target finding of DR 5-HT neurons. Dysregulation of CDH13 expression may thus contribute to alterations in this system of neurotransmission, impacting cognitive function, which is frequently impaired in neurodevelopmental disorders including attention-deficit/hyperactivity and autism spectrum disorders.},
  language  = {en}
}
@article{OehlerKistnerMartinetal.2017,
  author    = {Oehler, Beatrice and Kistner, Katrin and Martin, Corinna and Schiller, J{\"u}rgen and Mayer, Rafaela and Mohammadi, Milad and Sauer, Reine-Solange and Filipovic, Milos R. and Nieto, Francisco R. and Kloka, Jan and Pfl{\"u}cke, Diana and Hill, Kerstin and Schaefer, Michael and Malcangio, Marzia and Reeh, Peter W. and Brack, Alexander and Blum, Robert and Rittner, Heike L.},
  title     = {Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation},
  series = {Scientific Reports},
  volume    = {7},
  journal   = {Scientific Reports},
  number    = {5447},
  doi       = {10.1038/s41598-017-05348-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158536},
  year      = {2017},
  abstract  = {Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.},
  language  = {en}
}
@article{DombertBalkLueningschroeretal.2017,
  author    = {Dombert, Benjamin and Balk, Stefanie and L{\"u}ningschr{\"o}r, Patrick and Moradi, Mehri and Sivadasan, Rajeeve and Saal-Bauernschubert, Lena and Jablonka, Sibylle},
  title     = {BDNF/trkB induction of calcium transients through Ca\(_{v}\)2.2 calcium channels in motoneurons corresponds to F-actin assembly and growth cone formation on β2-chain laminin (221)},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {10},
  journal   = {Frontiers in Molecular Neuroscience},
  number    = {346},
  doi       = {10.3389/fnmol.2017.00346},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159094},
  year      = {2017},
  abstract  = {Spontaneous Ca\(^{2+}\) transients and actin dynamics in primary motoneurons correspond to cellular differentiation such as axon elongation and growth cone formation. Brain-derived neurotrophic factor (BDNF) and its receptor trkB support both motoneuron survival and synaptic differentiation. However, in motoneurons effects of BDNF/trkB signaling on spontaneous Ca\(^{2+}\) influx and actin dynamics at axonal growth cones are not fully unraveled. In our study we addressed the question how neurotrophic factor signaling corresponds to cell autonomous excitability and growth cone formation. Primary motoneurons from mouse embryos were cultured on the synapse specific, β2-chain containing laminin isoform (221) regulating axon elongation through spontaneous Ca\(^{2+}\) transients that are in turn induced by enhanced clustering of N-type specific voltage-gated Ca\(^{2+}\) channels (Ca\(_{v}\)2.2) in axonal growth cones. TrkB-deficient (trkBTK\(^{-/-}\)) mouse motoneurons which express no full-length trkB receptor and wildtype motoneurons cultured without BDNF exhibited reduced spontaneous Ca\(^{2+}\) transients that corresponded to altered axon elongation and defects in growth cone morphology which was accompanied by changes in the local actin cytoskeleton. Vice versa, the acute application of BDNF resulted in the induction of spontaneous Ca\(^{2+}\) transients and Ca\(_{v}\)2.2 clustering in motor growth cones, as well as the activation of trkB downstream signaling cascades which promoted the stabilization of β-actin via the LIM kinase pathway and phosphorylation of profilin at Tyr129. Finally, we identified a mutual regulation of neuronal excitability and actin dynamics in axonal growth cones of embryonic motoneurons cultured on laminin-221/211. Impaired excitability resulted in dysregulated axon extension and local actin cytoskeleton, whereas upon β-actin knockdown Ca\(_{v}\)2.2 clustering was affected. We conclude from our data that in embryonic motoneurons BDNF/trkB signaling contributes to axon elongation and growth cone formation through changes in the local actin cytoskeleton accompanied by increased Ca\(_{v}\)2.2 clustering and local calcium transients. These findings may help to explore cellular mechanisms which might be dysregulated during maturation of embryonic motoneurons leading to motoneuron disease.},
  language  = {en}
}
@article{MilanosElsharifJanzenetal.2017,
  author    = {Milanos, Sinem and Elsharif, Shaimaa A. and Janzen, Dieter and Buettner, Andrea and Villmann, Carmen},
  title     = {Metabolic Products of Linalool and Modulation of GABA\(_{A}\) Receptors},
  series = {Frontiers in Chemistry},
  volume    = {5},
  journal   = {Frontiers in Chemistry},
  number    = {46},
  doi       = {10.3389/fchem.2017.00046},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170779},
  year      = {2017},
  abstract  = {Terpenoids are major subcomponents in aroma substances which harbor sedative physiological potential. We have demonstrated that various monoterpenoids such as the acyclic linalool enhance GABAergic currents in an allosteric manner in vitro upon overexpression of inhibitory α1β2 GABA\(_{A}\) receptors in various expression systems. However, in plants or humans, i.e., following intake via inhalation or ingestion, linalool undergoes metabolic modifications including oxygenation and acetylation, which may affect the modulatory efficacy of the generated linalool derivatives. Here, we analyzed the modulatory potential of linalool derivatives at α1β2γ2 GABA\(_{A}\) receptors upon transient overexpression. Following receptor expression control, electrophysiological recordings in a whole cell configuration were used to determine the chloride influx upon co-application of GABA EC\(_{10-30}\) together with the modulatory substance. Our results show that only oxygenated linalool metabolites at carbon 8 positively affect GABAergic currents whereas derivatives hydroxylated or carboxylated at carbon 8 were rather ineffective. Acetylated linalool derivatives resulted in non-significant changes of GABAergic currents. We can conclude that metabolism of linalool reduces its positive allosteric potential at GABAA receptors compared to the significant potentiation effects of the parent molecule linalool itself.},
  language  = {en}
}
@article{LueningschroerBinottiDombertetal.2017,
  author    = {L{\"u}ningschr{\"o}r, Patrick and Binotti, Beyenech and Dombert, Benjamin and Heimann, Peter and Perez-Lara, Angel and Slotta, Carsten and Thau-Habermann, Nadine and von Collenberg, Cora R. and Karl, Franziska and Damme, Markus and Horowitz, Arie and Maystadt, Isabelle and F{\"u}chtbauer, Annette and F{\"u}chtbauer, Ernst-Martin and Jablonka, Sibylle and Blum, Robert and {\"U}{\c{c}}eyler, Nurcan and Petri, Susanne and Kaltschmidt, Barbara and Jahn, Reinhard and Kaltschmidt, Christian and Sendtner, Michael},
  title     = {Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron disease},
  series = {Nature Communications},
  volume    = {8},
  journal   = {Nature Communications},
  number    = {678},
  doi       = {10.1038/s41467-017-00689-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170048},
  year      = {2017},
  abstract  = {Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy of synaptic vesicles, which can be rescued by constitutively active Rab26. These findings define a mechanism for regulating autophagy in neurons that specifically targets synaptic vesicles. Disruption of this mechanism may contribute to the pathophysiology of several forms of motoneuron disease.},
  language  = {en}
}