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Lamina-specific restoration of serotonergic projections after Nogo-A antibody treatment of spinal cord injury in rats

Authors

  • Angela Müllner,

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    • *

      Present address: Brain Research Institute, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.

    • A.M. and R.R.G. contributed equally to this paper.

  • Roman R. Gonzenbach,

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    • A.M. and R.R.G. contributed equally to this paper.

  • Oli Weinmann,

    1. Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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  • Lisa Schnell,

    1. Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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  • Thomas Liebscher,

    1. Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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  • Martin E. Schwab

    1. Brain Research Institute, University of Zurich and Department of Biology, Swiss Federal Institute of Technology (ETH), Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
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Dr R.R. Gonzenbach, at *present address below.
E-mail: gonzenbach@hifo.uzh.ch

Abstract

Blocking the neurite growth inhibitor Nogo-A by neutralizing antibodies improves functional recovery after partial spinal cord injury. In parallel, regeneration and sprouting of cortico- and rubrospinal projections are increased and may partially explain the enhanced functional recovery. The serotonergic raphe-spinal tract, which plays a key regulatory role for spinal motor circuits, has not been analysed in detail with regard to its response to Nogo-A function blocking antibody treatment after spinal cord injury. We studied the effect of 2 weeks of intrathecal Nogo-A antibody application after partial thoracic spinal cord injury on the lamina-specific restitution of the serotonergic (5-HT) raphe-spinal projections to the mid-lumbar grey matter. Nine weeks after the lesion, the number of 5-HT fibres in Rexed's laminae 4 and 7 and the number of 5-HT-positive varicosities on motoneurons in lamina 9 returned to their lamina-specific preinjury levels in Nogo-A antibody-treated rats. By contrast, control antibody-treated animals showed only a moderate increase in 5-HT fibre density in the respective laminae, and the number of 5-HT-positive varicosities on motoneurons remained low. Our results suggest that the Nogo-A antibody-induced recovery of descending serotonergic projections to the grey matter is lamina-specific and molecular cues must be present to guide the growing axons to the correct target areas. This appropriate restitution of the serotonergic innervation below the lesion site probably contributes to the impressive recovery of motor function.

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