Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease

• DOI: 10.1093/brain/aws320
• Publication Date: 2013-10-23T21:19:59Z
• Authors: Marianna Bugiani; Nienke Postma; Emiel Polder; Nikki Dieleman; Peter G. Scheffer; Fraser J. Sim; Marjo S. van der ...; Ilja Boor
• Keywords: Gliosis

Vanishing white matter disease is a genetic leukoencephalopathy caused by mutations in eukaryotic translation initiation factor 2B. Patients experience slowly progressive neurological deterioration with episodes of rapid clinical worsening triggered stress.The may occur at any age and leads to early death.Characteristic neuropathological findings include cystic degeneration the feeble, if any, reactive gliosis, dysmorphic astrocytes paucity myelin despite an increase oligodendrocytic density.These features have been linked maturation defect oligodendrocytes.However, nature link between glial immaturity observed unclear.We hypothesized that defects function oligodendrocytes are related.Brain tissue seven patients genetically proven vanishing was investigated using immunohistochemistry, western blotting, quantitative polymerase chain reaction size exclusion chromatography.The results were compared those obtained from normal brain age-matched controls, chronic demyelinated multiple sclerosis lesions other acquired disorders.We found enriched CD44-expressing astrocyte precursor cells accumulates glycosaminoglycan hyaluronan.Hyaluronan major component extracellular matrix, CD44 hyaluronan receptor.We high molecular weight form overabundant, especially most severely affected areas.Comparison more frontal relatively spared cerebellum confirms accumulation pronounced than cerebellum.High known inhibit oligodendrocyte can explain arrested progenitor disease.In conclusion, species accumulate disease, inhibiting proper function, they be determinant pathology lack repair.