Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection

Epidural electrical stimulation (ES) of the lumbar spinal cord combined with daily locomotor training has been demonstrated to enhance stepping ability after complete spinal transection in rodents and clinically complete spinal injuries in humans. Although functional gain is observed, plasticity mec...

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Main Authors: Yazi D. Al’joboori, V. Reggie Edgerton, Ronaldo M. Ichiyama
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/10/11/824
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spelling doaj-a72f6e43d59a4a648668a57b660626e72020-11-25T04:00:16ZengMDPI AGBrain Sciences2076-34252020-11-011082482410.3390/brainsci10110824Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord TransectionYazi D. Al’joboori0V. Reggie Edgerton1Ronaldo M. Ichiyama2Faculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UKPhysiological Science, Neurobiology and Brain Research Institute, University of California, Los Angeles, CA 90095, USAFaculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UKEpidural electrical stimulation (ES) of the lumbar spinal cord combined with daily locomotor training has been demonstrated to enhance stepping ability after complete spinal transection in rodents and clinically complete spinal injuries in humans. Although functional gain is observed, plasticity mechanisms associated with such recovery remain mostly unclear. Here, we investigated how ES and locomotor training affected expression of chondroitin sulfate proteoglycans (CSPG), perineuronal nets (PNN), and synaptic plasticity on spinal motoneurons. To test this, adult rats received a complete spinal transection (T9–T10) followed by daily locomotor training performed under ES with administration of quipazine (a serotonin (5-HT) agonist) starting 7 days post-injury (dpi). Excitatory and inhibitory synaptic changes were examined at 7, 21, and 67 dpi in addition to PNN and CSPG expression. The total amount of CSPG expression significantly increased with time after injury, with no effect of training. An interesting finding was that γ-motoneurons did not express PNNs, whereas α-motoneurons demonstrated well-defined PNNs. This remarkable difference is reflected in the greater extent of synaptic changes observed in γ-motoneurons compared to α-motoneurons. A medium negative correlation between CSPG expression and changes in putative synapses around α-motoneurons was found, but no correlation was identified for γ-motoneurons. These results suggest that modulation of γ-motoneuron activity is an important mechanism associated with functional recovery induced by locomotor training under ES after a complete spinal transection.https://www.mdpi.com/2076-3425/10/11/824spinal cord injuryrehabilitationchondroitin sulfate proteoglycansneuromodulationgamma motoneuron
collection DOAJ
language English
format Article
sources DOAJ
author Yazi D. Al’joboori
V. Reggie Edgerton
Ronaldo M. Ichiyama
spellingShingle Yazi D. Al’joboori
V. Reggie Edgerton
Ronaldo M. Ichiyama
Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection
Brain Sciences
spinal cord injury
rehabilitation
chondroitin sulfate proteoglycans
neuromodulation
gamma motoneuron
author_facet Yazi D. Al’joboori
V. Reggie Edgerton
Ronaldo M. Ichiyama
author_sort Yazi D. Al’joboori
title Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection
title_short Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection
title_full Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection
title_fullStr Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection
title_full_unstemmed Effects of Rehabilitation on Perineural Nets and Synaptic Plasticity Following Spinal Cord Transection
title_sort effects of rehabilitation on perineural nets and synaptic plasticity following spinal cord transection
publisher MDPI AG
series Brain Sciences
issn 2076-3425
publishDate 2020-11-01
description Epidural electrical stimulation (ES) of the lumbar spinal cord combined with daily locomotor training has been demonstrated to enhance stepping ability after complete spinal transection in rodents and clinically complete spinal injuries in humans. Although functional gain is observed, plasticity mechanisms associated with such recovery remain mostly unclear. Here, we investigated how ES and locomotor training affected expression of chondroitin sulfate proteoglycans (CSPG), perineuronal nets (PNN), and synaptic plasticity on spinal motoneurons. To test this, adult rats received a complete spinal transection (T9–T10) followed by daily locomotor training performed under ES with administration of quipazine (a serotonin (5-HT) agonist) starting 7 days post-injury (dpi). Excitatory and inhibitory synaptic changes were examined at 7, 21, and 67 dpi in addition to PNN and CSPG expression. The total amount of CSPG expression significantly increased with time after injury, with no effect of training. An interesting finding was that γ-motoneurons did not express PNNs, whereas α-motoneurons demonstrated well-defined PNNs. This remarkable difference is reflected in the greater extent of synaptic changes observed in γ-motoneurons compared to α-motoneurons. A medium negative correlation between CSPG expression and changes in putative synapses around α-motoneurons was found, but no correlation was identified for γ-motoneurons. These results suggest that modulation of γ-motoneuron activity is an important mechanism associated with functional recovery induced by locomotor training under ES after a complete spinal transection.
topic spinal cord injury
rehabilitation
chondroitin sulfate proteoglycans
neuromodulation
gamma motoneuron
url https://www.mdpi.com/2076-3425/10/11/824
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AT vreggieedgerton effectsofrehabilitationonperineuralnetsandsynapticplasticityfollowingspinalcordtransection
AT ronaldomichiyama effectsofrehabilitationonperineuralnetsandsynapticplasticityfollowingspinalcordtransection
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