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


Müllner, A; Gonzenbach, R R; Weinmann, O; Schnell, L; Liebscher, T; Schwab, M E (2008). Lamina-specific restoration of serotonergic projections after Nogo-A antibody treatment of spinal cord injury in rats. European Journal of Neuroscience, 27(2):326-333.

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.

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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30 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:15 Dec 2008 16:20
Last Modified:05 Apr 2016 12:40
Publisher:Wiley-Blackwell
ISSN:0953-816X
Publisher DOI:https://doi.org/10.1111/j.1460-9568.2007.06006.x
PubMed ID:18215231

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