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.

• Klíčová slova
• extracellular diffusion, extracellular matrix, extracellular transmission, hyaluronan synthase, perineuronal nets, plasticity,
• MeSH
• astrocyty účinky léků   MeSH
• extracelulární matrix * účinky léků   metabolismus   patologie   MeSH
• extracelulární prostor * účinky léků   metabolismus   MeSH
• gliový fibrilární kyselý protein metabolismus   MeSH
• hymekromon farmakologie   MeSH
• krysa rodu Rattus MeSH
• kyselina hyaluronová metabolismus   MeSH
• mozek * účinky léků   metabolismus   MeSH
• nervová síť * účinky léků   patologie   MeSH
• potkani Sprague-Dawley MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• gliový fibrilární kyselý protein MeSH
• hymekromon MeSH
• kyselina hyaluronová MeSH

BACKGROUND: Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. PURPOSE: To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. STUDY TYPE: Prospective technical development. POPULATION: Three oils with different n-3 FA content and 24 healthy subjects. FIELD STRENGTH/SEQUENCE: Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. ASSESSMENT: Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. STATISTICAL TESTS: SVS data were compared to gas chromatography with the Pearson correlation coefficient. RESULTS: T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). DATA CONCLUSION: PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.

• Klíčová slova
• 7 T, T2 relaxation, in vivo MRS, long TE, n-3 fatty acids,
• MeSH
• dospělí MeSH
• fantomy radiodiagnostické MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie * MeSH
• omega-3 mastné kyseliny chemie   MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• počítačová simulace MeSH
• podkožní tuk diagnostické zobrazování   MeSH
• poměr signál - šum MeSH
• prospektivní studie MeSH
• senioři MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• omega-3 mastné kyseliny MeSH