Abnormal morphology of peripheral cell tissues from patients with Huntington disease

Ferdinando Squitieri, Alessandra Falleni, Milena Cannella, Sara Orobello, Federica Fulceri, Paola Lenzi, Francesco Fornai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalJournal of Neural Transmission
Volume117
Issue number1
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Autophagy
  • Electron microscopy
  • Fibroblasts
  • Homozygous Huntington disease
  • Mitochondria
  • Myoblasts
  • Peripheral tissues

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

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