Abnormal morphology of peripheral cell tissues from patients with Huntington disease
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We investigated the genotype-dependency of morphological abnormalities in peripheral cells from Huntington disease (HD) patients. Cell cultures derived from skin and muscle biopsies showed a different set of abnormalities depending on the genotype (i.e. heterozygous and homozygous for CAG mutations) and the tissue (i.e. fibroblasts and myoblasts). In general, homozygotes’ cell lines showed massive ultrastructural damage of specific cell organelles compared with age matched control. These consist of vacuolization, deranged crests and matrix found within giant mitochondria. In addition, enlarged endoplasmic reticulum and the occurrence of numerous autophagic vacuoles, which were similar to those occurring in neurons within affected brain areas, were described. Despite a comparable dose-dependency on mitochondrial changes, this kind of alterations differ in fibroblasts compared with myoblasts. In fact, the internal mitochondrial structure was merely lost in myoblasts, while it shows pathological re-organization within fibroblasts, where altered crests appear as multilamellar circles. These data indicate that ultrastructural abnormalities from peripheral tissues of HD patients can be used as potential disease markers which are easier to get than autoptic brains. Moreover, the occurrence of ultrastructural cell pathology reminiscent of neuronal degeneration in HD, suggests the use of human peripheral cells as a tool to investigate the pathogenic cascade subsequent to huntingtin dysregulation.
KeywordsAutophagy Electron microscopy Fibroblasts Homozygous Huntington disease Mitochondria Myoblasts Peripheral tissues
We thank the European Huntington’s Disease Network, all patients and their families (Associazione Italiana Corea di Huntington-Neuromed) and the Italian Society of Neurologists (SNO––Lascito Gobessi), for their kind cooperation and support to FS. The financial support of Telethon––Italy to FS (Grant no. GGP06181), is gratefully acknowledged. The financial support of Monte dei Paschi di Siena to the Department of Human Morphology and Applied Biology, University of Pisa is gratefully acknowledged.
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