Emmanuel Brouillet1, Marie‐Caroline Guyot1, Vincent Mittoux1, Séverine Altairac1, Françoise Condé1, Stéphane Palfi1, Philippe Hantraye1
1Service Hospitalier Frédéric Joliot, Unité de Recherche Associée 2210, Commissariat à l'Energie Atomique‐Centre National de la Recherche Scientifique, Département de Recherche Médicale, Direction des Sciences du Vivant, Orsay, France
Tóm tắt
Abstract: Chronic inhibition of succinate dehydrogenase (SDH) by systemic injection of the selective inhibitor 3‐nitropropionic acid (3NP) has been used as an animal model for Huntington's disease (HD). However, the mechanisms by which 3NP produces lesions in the striatum are not fully characterized. A quantitative histochemical method was developed to study the level of regional SDH inhibition resulting from intraperitoneal injection of 3NP or chronic intoxication using osmotic pumps. The results showed that (a) 3NP was an irreversible SDH inhibitor in vivo, (b) the level of SDH inhibition in the striatum (the brain region most vulnerable to 3NP) was similar to that observed in other brain regions not affected by the toxin, such as the cerebral cortex, and (c) the neurotoxic threshold of SDH inhibition in the brain was 50–60% of control levels. The present study demonstrates that the selective degeneration in the striatum observed after chronic 3NP administration cannot be ascribed to a preferential inhibition of SDH in this particular brain region. This work also suggests that the partial decrease in the activity of the respiratory chain complex II–III reported in HD patients may be sufficient to induce the selective striatal degeneration observed in this disorder.
