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Disruption of Extracellular Matrix and Perineuronal Nets Modulates Extracellular Space Volume and Geometry
E. Syková, I. Voříšek, Z. Starčuk, J. Kratochvíla, I. Pavlova, Y. Ichikawa, JCF. Kwok, E. Kmoníčková, S. Myronchenko, T. Hromádka, T. Smolek, M. Avila, N. Basheer, N. Žilka
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
NLK
Open Access Digital Library
od 1981-01-01
Open Access Digital Library
od 1981-01-01
- MeSH
- astrocyty metabolismus MeSH
- chondroitinsulfát proteoglykany metabolismus MeSH
- extracelulární matrix * metabolismus MeSH
- extracelulární prostor * metabolismus MeSH
- gliový fibrilární kyselý protein metabolismus MeSH
- hymekromon farmakologie MeSH
- krysa rodu rattus MeSH
- kyselina hyaluronová MeSH
- mozek metabolismus MeSH
- nervová síť účinky léků diagnostické zobrazování MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Extracellular matrix (ECM) is a network of macromolecules which has two forms-perineuronal nets (PNNs) and a diffuse ECM (dECM)-both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility. Two months after oral treatment of rats with 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan (HA) synthesis, we found downregulated staining for PNNs, HA, chondroitin sulfate proteoglycans, and glial fibrillary acidic protein. These changes were enhanced after 4 and 6 months and were reversible after a normal diet. Morphometric analysis further indicated atrophy of astrocytes. Using real-time iontophoretic method dysregulation of ECM resulted in increased ECS volume fraction α in the somatosensory cortex by 35%, from α = 0.20 in control rats to α = 0.27 after the 4-MU diet. Diffusion-weighted magnetic resonance imaging revealed a decrease of mean diffusivity and fractional anisotropy (FA) in the cortex, hippocampus, thalamus, pallidum, and spinal cord. This study shows the increase in ECS volume, a loss of FA, and changes in astrocytes due to modulation of PNNs and dECM that could affect extrasynaptic transmission, cell-to-cell communication, and neural plasticity.
Department of Pharmacology 2nd Faculty of Medicine Charles University Prague 15000 Czech Republic
Institute of Neuroimmunology Slovak Academy of Science Bratislava 84510 Slovakia
Institute of Scientific Instruments Czech Academy of Sciences Brno 61200 Czech Republic
Citace poskytuje Crossref.org
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- $a Extracellular matrix (ECM) is a network of macromolecules which has two forms-perineuronal nets (PNNs) and a diffuse ECM (dECM)-both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility. Two months after oral treatment of rats with 4-methylumbelliferone (4-MU), an inhibitor of hyaluronan (HA) synthesis, we found downregulated staining for PNNs, HA, chondroitin sulfate proteoglycans, and glial fibrillary acidic protein. These changes were enhanced after 4 and 6 months and were reversible after a normal diet. Morphometric analysis further indicated atrophy of astrocytes. Using real-time iontophoretic method dysregulation of ECM resulted in increased ECS volume fraction α in the somatosensory cortex by 35%, from α = 0.20 in control rats to α = 0.27 after the 4-MU diet. Diffusion-weighted magnetic resonance imaging revealed a decrease of mean diffusivity and fractional anisotropy (FA) in the cortex, hippocampus, thalamus, pallidum, and spinal cord. This study shows the increase in ECS volume, a loss of FA, and changes in astrocytes due to modulation of PNNs and dECM that could affect extrasynaptic transmission, cell-to-cell communication, and neural plasticity.
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