TY - JOUR
T1 - Voluntary wheel running preserves lumbar perineuronal nets, enhances motor functions and prevents hyperreflexia after spinal cord injury
AU - Sánchez-Ventura, J.
AU - Giménez-Llort, L.
AU - Penas, C.
AU - Udina, E.
N1 - Funding Information:
This work was funded by the Fundació La Marató-TV3 ( TV3-201736-30-31, Catalunya, Spain ).
Funding Information:
The authors research was supported by funds from spanish CIBERNED and TERCEL networks, co-funded by European Union (ERDF/ESF, “Investing in your future”). JSV holds a predoctoral fellowship of the AGAUR, Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement de la Generalitat de Catalunya, Spain, cofunded by European Social Funds .
Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Perineuronal nets (PNN) are a promising candidate to harness neural plasticity since their activity-dependent modulation allows to either stabilize the circuits or increase plasticity. Modulation of plasticity is the basis of rehabilitation strategies to reduce maladaptive plasticity after spinal cord injuries (SCI). Hence, it is important to understand how spinal PNN are affected after SCI and rehabilitation. Thus, this work aims to describe functional and PNN changes after thoracic SCI in mice, followed by different activity-dependent therapies: enriched environment, voluntary wheel and forced treadmill running. We found that the contusion provoked thermal hyperalgesia, hyperreflexia and locomotor impairment as measured by thermal plantar test, H wave recordings and the BMS score of locomotion, respectively. In the spinal cord, SCI reduced PNN density around lumbar motoneurons. In contrast, activity-based therapies increased motoneuron activity and reversed PNN decrease. The voluntary wheel group showed full preservation of PNN which also correlated with reduced hyperreflexia and better locomotor recovery. Furthermore, both voluntary wheel and treadmill running reduced hyperalgesia, but this finding was independent of lumbar PNN levels. In the brainstem sensory nuclei, SCI did not modify PNN whereas some activity-based therapies reduced them. The results of the present study highlight the impact of SCI on decreasing PNN at caudal segments of the spinal cord and the potential of physical activity-based therapies to reverse PNN disaggregation and to improve functional recovery. As modulating plasticity is crucial for restoring damaged neural circuits, regulating PNN by activity is an encouraging target to improve the outcome after injury.
AB - Perineuronal nets (PNN) are a promising candidate to harness neural plasticity since their activity-dependent modulation allows to either stabilize the circuits or increase plasticity. Modulation of plasticity is the basis of rehabilitation strategies to reduce maladaptive plasticity after spinal cord injuries (SCI). Hence, it is important to understand how spinal PNN are affected after SCI and rehabilitation. Thus, this work aims to describe functional and PNN changes after thoracic SCI in mice, followed by different activity-dependent therapies: enriched environment, voluntary wheel and forced treadmill running. We found that the contusion provoked thermal hyperalgesia, hyperreflexia and locomotor impairment as measured by thermal plantar test, H wave recordings and the BMS score of locomotion, respectively. In the spinal cord, SCI reduced PNN density around lumbar motoneurons. In contrast, activity-based therapies increased motoneuron activity and reversed PNN decrease. The voluntary wheel group showed full preservation of PNN which also correlated with reduced hyperreflexia and better locomotor recovery. Furthermore, both voluntary wheel and treadmill running reduced hyperalgesia, but this finding was independent of lumbar PNN levels. In the brainstem sensory nuclei, SCI did not modify PNN whereas some activity-based therapies reduced them. The results of the present study highlight the impact of SCI on decreasing PNN at caudal segments of the spinal cord and the potential of physical activity-based therapies to reverse PNN disaggregation and to improve functional recovery. As modulating plasticity is crucial for restoring damaged neural circuits, regulating PNN by activity is an encouraging target to improve the outcome after injury.
KW - Activity-dependent therapy
KW - Hyperreflexia
KW - Motoneurons
KW - Neuropathic pain
KW - Perineuronal nets
KW - Physical activity
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85097522660&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2020.113533
DO - 10.1016/j.expneurol.2020.113533
M3 - Artículo
C2 - 33264633
AN - SCOPUS:85097522660
VL - 336
M1 - 113533
ER -