Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease
| Autor: | Marianna Bugiani, Nienke L. Postma, Marjo S. van der Knaap, Ilja Boor, Peter G. Scheffer, Emiel Polder, Fraser J. Sim, Nikki Dieleman |
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| Přispěvatelé: | Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Other departments, Pathology, Pediatric surgery, NCA - Brain mechanisms in health and disease, Laboratory Medicine, ICaR - Circulation and metabolism |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Multiple Sclerosis Adolescent Biology Nerve Fibers Myelinated Leukoencephalopathy White matter Myelin Leukoencephalopathies medicine Humans Hyaluronic Acid Child Aged Glial fibrillary acidic protein Multiple sclerosis Brain Infant Cell Differentiation SDG 10 - Reduced Inequalities Middle Aged medicine.disease Hyaluronan-mediated motility receptor Oligodendrocyte Oligodendroglia medicine.anatomical_structure Child Preschool biology.protein Female Neurology (clinical) Astrocyte |
| Zdroj: | Bugiani, M, Postma, N L, Polder, E, Dieleman, N, Scheffer, P G, Sim, F J, van der Knaap, M S & Boor, P K I 2013, ' Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease ', Brain, vol. 136, pp. 209-222 . https://doi.org/10.1093/brain/aws320 Brain, 136, 209-222. Oxford University Press Brain, 136(1), 209-222. Oxford University Press |
| ISSN: | 0006-8950 |
| Popis: | Vanishing white matter disease is a genetic leukoencephalopathy caused by mutations in eukaryotic translation initiation factor 2B. Patients experience a slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered by stress. The disease may occur at any age and leads to early death. Characteristic neuropathological findings include cystic degeneration of the white matter with feeble, if any, reactive gliosis, dysmorphic astrocytes and paucity of myelin despite an increase in oligodendrocytic density. These features have been linked to a maturation defect of astrocytes and oligodendrocytes. However, the nature of the link between glial immaturity and the observed neuropathological features is unclear. We hypothesized that the defects in maturation and function of astrocytes and oligodendrocytes are related. Brain tissue of seven patients with genetically proven vanishing white matter disease was investigated using immunohistochemistry, western blotting, quantitative polymerase chain reaction and size exclusion chromatography. The results were compared with those obtained from normal brain tissue of age-matched controls, from chronic demyelinated multiple sclerosis lesions and from other genetic and acquired white matter disorders. We found that the white matter of patients with vanishing white matter disease is enriched in CD44-expressing astrocyte precursor cells and accumulates the glycosaminoglycan hyaluronan. Hyaluronan is a major component of the extracellular matrix, and CD44 is a hyaluronan receptor. We found that a high molecular weight form of hyaluronan is overabundant, especially in the most severely affected areas. Comparison between the more severely affected frontal white matter and the relatively spared cerebellum confirms that high molecular weight hyaluronan accumulation is more pronounced in the frontal white matter than in the cerebellum. High molecular weight hyaluronan is known to inhibit astrocyte and oligodendrocyte precursor maturation and can explain the arrested glial progenitor maturation observed in vanishing white matter disease. In conclusion, high molecular weight species of hyaluronan accumulate in the white matter of patients with vanishing white matter disease, and by inhibiting glial maturation and proper function, they may be a major determinant of the white matter pathology and lack of repair. * Abbreviations : eIF : eukaryotic translation initiation factor GFAP : glial fibrillary acidic protein HABP : hyaluronan-binding protein VWM : vanishing white matter disease |
| Databáze: | OpenAIRE |
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