Low oral dose of 4-methylumbelliferone reduces glial scar but is insufficient to induce functional recovery after spinal cord injury

0582281 - ÚEM 2024 RIV US eng J - Journal Article
Štěpánková, Kateřina - Chudíčková, Milada - Šimková, Zuzana - Martinez-Varea, Noelia - Kubinová, Šárka - Machová-Urdzíková, Lucia - Jendelová, Pavla - Kwok, Jessica
Low oral dose of 4-methylumbelliferone reduces glial scar but is insufficient to induce functional recovery after spinal cord injury.
Scientific Reports. Roč. 13, č. 1 (2023), č. článku 19183. ISSN 2045-2322. E-ISSN 2045-2322
R&D Projects: GA MŠMT(CZ) EF15_003/0000419; GA ČR(CZ) GA19-10365S; GA MŠMT(CZ) LM2023050
Institutional support: RVO:68378041
Keywords : extracellular-matrix * hyaluronan synthesis * serotonergic * neurons * chondroitin sulfate * plateau potential
OECD category: Neurosciences (including psychophysiology
Impact factor: 4.6, year: 2022
Method of publishing: Open access
https://www.nature.com/articles/s41598-023-46539-5

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.
Permanent Link: https://hdl.handle.net/11104/0350386