Modeling the natural history of Pelizaeus–Merzbacher disease
| Autor: | Joshua A. Mayer, Ian D. Duncan, Elizabeth Cooksey, Abigail B. Radcliff, Ian R. Griffiths, Chelsey M. Smith, James E. Goldman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Proteolipid protein 1 Pelizaeus-Merzbacher Disease Disease Biology Article Axon lcsh:RC321-571 Myelin PLP1 Dogs medicine Animals Myelin Proteolipid Protein lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Myelin Sheath X-linked Cell Death Endoplasmic reticulum Pelizaeus–Merzbacher disease Brain medicine.disease Oligodendrocyte Axons Myelin proteolipid protein Disease Models Animal Oligodendroglia medicine.anatomical_structure Neurology Spinal Cord Astrocytes Mutation Disease Progression Female Neuroscience Hypomyelination |
| Zdroj: | Neurobiology of Disease, Vol 75, Iss, Pp 115-130 (2015) |
| Popis: | Major gaps in our understanding of the leukodystrophies result from their rarity and the lack of tissue for the interdisciplinary studies required to extend our knowledge of the pathophysiology of the diseases. This study details the natural evolution of changes in the CNS of the shaking pup (shp), a model of the classical form of the X-linked disorder Pelizaeus–Merzbacher disease, in particular in glia, myelin, and axons, which is likely representative of what occurs over time in the human disease. The mutation in the proteolipid protein gene, PLP1, leads to a delay in differentiation, increased cell death, and a marked distension of the rough endoplasmic reticulum in oligodendrocytes. However, over time, more oligodendrocytes differentiate and survive in the spinal cord leading to an almost total recovery of myelination, In contrast, the brain remains persistently hypomyelinated. These data suggest that shp oligodendrocytes may be more functional than previously realized and that their early recruitment could have therapeutic value. |
| Databáze: | OpenAIRE |
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