Spinal cord injury (SCI) induces the upregulation of chondroitin sulfate proteoglycans (CSPGs) at the glial scar and inhibits neuroregeneration. Under normal physiological condition, CSPGs interact with hyaluronan (HA) and other extracellular matrix on the neuronal surface forming a macromolecular structure called perineuronal nets (PNNs) which regulate neuroplasticity. 4-methylumbelliferone (4-MU) is a known inhibitor for HA synthesis but has not been tested in SCI. We first tested the effect of 4-MU in HA reduction in uninjured rats. After 8 weeks of 4-MU administration at a dose of 1.2 g/kg/day, we have not only observed a reduction of HA in the uninjured spinal cords but also a down-regulation of CS glycosaminoglycans (CS-GAGs). In order to assess the effect of 4-MU in chronic SCI, six weeks after Th8 spinal contusion injury, rats were fed with 4-MU or placebo for 8 weeks in combination with daily treadmill rehabilitation for 16 weeks to promote neuroplasticity. 4-MU treatment reduced the HA synthesis by astrocytes around the lesion site and increased sprouting of 5-hydroxytryptamine fibres into ventral horns. However, the current dose was not sufficient to suppress CS-GAG up-regulation induced by SCI. Further adjustment on the dosage will be required to benefit functional recovery after SCI.

• MeSH
• chondroitinsulfát proteoglykany MeSH
• glióza * patologie   MeSH
• hymekromon terapeutické užití   MeSH
• krysa rodu Rattus MeSH
• kyselina hyaluronová MeSH
• mícha patologie   MeSH
• poranění míchy * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chondroitinsulfát proteoglykany MeSH
• hymekromon MeSH
• kyselina hyaluronová MeSH

Perineuronal nets (PNNs) are extracellular matrix structures surrounding neuronal sub-populations throughout the central nervous system, regulating plasticity. Enzymatically removing PNNs successfully enhances plasticity and thus functional recovery, particularly in spinal cord injury models. While PNNs within various brain regions are well studied, much of the composition and associated populations in the spinal cord is yet unknown. We aim to investigate the populations of PNN neurones involved in this functional motor recovery. Immunohistochemistry for choline acetyltransferase (labelling motoneurones), PNNs using Wisteria floribunda agglutinin (WFA) and chondroitin sulphate proteoglycans (CSPGs), including aggrecan, was performed to characterise the molecular heterogeneity of PNNs in rat spinal motoneurones (Mns). CSPG-positive PNNs surrounded ~70-80% of Mns. Using WFA, only ~60% of the CSPG-positive PNNs co-localised with WFA in the spinal Mns, while ~15-30% of Mns showed CSPG-positive but WFA-negative PNNs. Selective labelling revealed that aggrecan encircled ~90% of alpha Mns. The results indicate that (1) aggrecan labels spinal PNNs better than WFA, and (2) there are differences in PNN composition and their associated neuronal populations between the spinal cord and cortex. Insights into the role of PNNs and their molecular heterogeneity in the spinal motor pools could aid in designing targeted strategies to enhance functional recovery post-injury.

• Klíčová slova
• alpha motoneurone, chondroitin sulphate proteoglycans, gamma motoneurone, perineuronal nets, spinal cord,
• MeSH
• cholin-O-acetyltransferasa metabolismus   MeSH
• chondroitinsulfát proteoglykany metabolismus   MeSH
• extracelulární matrix - proteiny metabolismus   MeSH
• extracelulární matrix metabolismus   MeSH
• krysa rodu Rattus MeSH
• mícha cytologie   metabolismus   MeSH
• motorické neurony cytologie   metabolismus   MeSH
• neuroplasticita MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cholin-O-acetyltransferasa MeSH
• chondroitinsulfát proteoglykany MeSH
• extracelulární matrix - proteiny MeSH