Buccal epithelial cells as potential non-invasive materials for the monitoring of mitochondrial disturbances to track Huntington's disease progression : a pilot study
Abstrakt
Introduction: Huntington's disease (HD) is an incurable neurodegenerative disorder that manifests progressive behavioral and motoric changes and cognitive dysfunction. It is caused by CAG expansion in huntingtin gene and has almost full penetrance.
The striatum is the most affected tissue in HD, but pathological changes are also detected in the peripheral tissues like blood, skeletal muscle or fibroblasts. Intensive HD research in the last years has revealed an important role of mitochondrial dysfunction in the pathogenesis and progression of the disease, which includes changes in the activity of the respiratory chain complexes, ATP synthesis or increased apoptotic stimuli.
Aim and material: We decided to analyse the amount of mitochondrial respiratory chain complex I and IV in the epithelial cells of buccal smear in six HD patients and from an animal disease model, minipigs transgenic for the N-terminal part of human mutated huntingtin (TgHD). Methods: The amount of mitochondrial complexes I and IV was determined by dipstick microimmunocapture assay (Mitosciences).
Results: A decreased level of CI and/or CIV in HD patients (4/6), up to 36% of the control values, was detected. The analysis performed on the minipig samples showed strong signals, but no uniform trend was observed within the WT and TgHD groups at the age of 36 months.
Conclusions: The advantage of this approach is that samples of buccal cells can be collected repeatedly without the stress for the studied objects and therefore can serve for longitudinal monitoring of mitochondria during the asymptomatic stage until full development of the disease