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Pre-neurodegeneration of mitral cells in the pcd mutant mouse is associated with DNA damage, transcriptional repression, and reorganization of nuclear speckles and Cajal bodies

AuthorsValero, Jorge; Berciano, María T.; Weruaga, Eduardo; Lafarga, Miguel; Alonso, José R.
Issue Date2006
CitationMolecular and Cellular Neurosciences 33(3): 283-295 (2006)
AbstractDNA damage and impairment of its repair underlie several neurodegenerative diseases. The Purkinje cell degeneration (pcd) mutation causes the loss of Nna1 expression and is associated with a selective and progressive degeneration of specific neuronal populations, including mitral cells in the olfactory bulb. Using an in situ transcription assay, molecular markers for both nuclear compartments and components of the DNA damage/repair pathway, and ultrastructural analysis, here we demonstrate that the pcd mutation induces the formation of DNA damage/repair foci in mitral cells. Furthermore, this effect is associated with transcriptional inhibition, heterochromatinization, nucleolar segregation and the reorganization of nuclear speckles of splicing factors and Cajal bodies. The most significant cytoplasmic alteration observed was a partial replacement of rough endoplasmic reticulum cisternae by a larger amount of free ribosomes, while other organelles were structurally preserved. The tools employed in this work may be of use for the early detection of predegenerative processes in neurodegenerative disorders and for validating rescue strategies. © 2006 Elsevier Inc. All rights reserved.
Identifiersdoi: 10.1016/j.mcn.2006.08.002
issn: 1044-7431
Appears in Collections:(IBBTEC) Artículos
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