60449ec94dca8793911a151fd1d89964 pmc_11050079.pdf 08dd7c62b5a73700c9245e64e1c4765753764019 pmc_11050079.pdf 0a67b0119a8dcbe011b9de385f2ce9901be8e562bb4c01c1ae35f4ae610b780d pmc_11050079.pdf Title: Link Protein 1 Is Involved in the Activity-Dependent Modulation of Perineuronal Nets in the Spinal Cord Subject: 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 inspinal circuits. Keywords: perineuronal nets; spinal cord injury; link protein 1; activity-dependent therapy;maladaptive plasticity Author: Judith Sánchez-Ventura, Natalia Lago, Clara Penas, Xavier Navarro and Esther Udina Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Apr 12 08:39:20 2024 CEST ModDate: Fri Apr 12 08:47:45 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3791409 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- KLSDJL+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 PAYTUQ+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 VUYJDQ+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 DRZUJM+VnURWPalladioL Type 1 Custom yes yes no 23 0 AIQCCL+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 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238 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 242 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 249 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 256 0 RMKZIE+Dingbats Type 1 Builtin yes yes no 289 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-15 03:23:48 CEST RepresentationInformation: pmc_11050079.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-05-15 02:37:37 CEST Size: 3791409 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 517 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Link Protein 1 Is Involved in the Activity-Dependent Changes of Perineuronal Nets in the Spinal Cord Destination: subsection.2.1 Item: Title: Uninjured Crtl1 Knock-Out Mice Mimic the Functional Outcomes Observed in the Injured Wild-Type Mice Destination: subsection.2.2 Item: Title: Lack of Modulation of Perineuronal Nets after Spinal Cord Injury in Crtl1 Knock-Out Mice Destination: subsection.2.3 Item: Title: Lack of Link Protein 1 Modifies Glial Reactivity after Spinal Cord Injury Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Children: Item: Title: Link Protein 1 Mediates the Activity-Dependent Remodeling of Perineuronal Nets Destination: subsection.3.1 Children: Item: Title: Remodeling of Spinal Perineuronal Nets after a Locomotor Activity Destination: subsubsection.3.1.1 Item: Title: Remodeling of Spinal Perineuronal Nets after Spinal Cord Injury Destination: subsubsection.3.1.2 Item: Title: Link Protein 1 Plays a Role in Neural Excitability Destination: subsection.3.2 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Experimental Groups Destination: subsection.4.1 Item: Title: Spinal Cord Injury Destination: subsection.4.2 Item: Title: Activity-Based Therapy Protocol Destination: subsection.4.3 Item: Title: Functional Assessment Destination: subsection.4.4 Children: Item: Title: Locomotion Assessment Destination: subsubsection.4.4.1 Item: Title: Algesimetry Tests Destination: subsubsection.4.4.2 Item: Title: Electrophysiological Tests Destination: subsubsection.4.4.3 Item: Title: Histological Evaluation Destination: subsection.4.5 Item: Title: Statistical Analysis Destination: subsection.4.6 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.A. Info: Title: Link Protein 1 Is Involved in the Activity-Dependent Modulation of Perineuronal Nets in the Spinal Cord Author: Judith Sánchez-Ventura, Natalia Lago, Clara Penas, Xavier Navarro and Esther Udina Subject: 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 inspinal circuits. 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