Link Protein 1 Is Involved in the Activity-Dependent Modulation of Perineuronal Nets in the Spinal Cord

One of the challenges of the mature nervous system is to maintain the stability of neural networks while providing a degree of plasticity to generate experience-dependent modifications. This plasticity-stability dynamism is regulated by perineuronal nets (PNNs) and is crucial for the proper function...

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Detalhes bibliográficos
Autores: Sánchez-Ventura, Judith|||0000-0001-6143-0440, Lago, Natalia|||0000-0002-5631-8558, Penas Pérez, Clara|||0000-0003-0554-3832, Navarro, X. (Xavier)|||0000-0001-9849-902X, Udina i Bonet, Esther|||0000-0003-1954-8562
Formato: artículo
Fecha de publicación:2024
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:292054
Acesso em linha:https://ddd.uab.cat/record/292054
https://dx.doi.org/urn:doi:10.3390/ijms25084267
Access Level:acceso abierto
Palavra-chave:Activity-dependent therapy
Link protein 1
Maladaptive plasticity
Perineuronal nets
Spinal cord injury
Descrição
Resumo:One of the challenges of the mature nervous system is to maintain the stability of neural networks while providing a degree of plasticity to generate experience-dependent modifications. This plasticity-stability dynamism is regulated by perineuronal nets (PNNs) and is crucial for the proper functioning of the system. Previously, we found a relation between spinal PNNs reduction and maladaptive plasticity after spinal cord injury (SCI), which was attenuated by maintaining PNNs with activity-dependent therapies. Moreover, transgenic mice lacking the cartilage link protein 1 (Crtl1 KO mice) showed aberrant spinal PNNs and increased spinal plasticity. Therefore, the aim of this study is to evaluate the role of link protein 1 in the activity-dependent modulation of spinal PNNs surrounding motoneurons and its impact on the maladaptive plasticity observed following SCI. We first studied the activity-dependent modulation of spinal PNNs using a voluntary wheel-running protocol. This training protocol increased spinal PNNs in WT mice but did not modify PNN components in Crtl1 KO mice, suggesting that link protein 1 mediates the activity-dependent modulation of PNNs. Secondly, a thoracic SCI was performed, and functional outcomes were evaluated for 35 days. Interestingly, hyperreflexia and hyperalgesia found at the end of the experiment in WT-injured mice were already present at basal levels in Crtl1 KO mice and remained unchanged after the injury. These findings demonstrated that link protein 1 plays a dual role in the correct formation and in activity-dependent modulation of PNNs, turning it into an essential element for the proper function of PNN in spinal circuits.