Old mice present increased levels of succinate dehydrogenase activity and lower vulnerability to dyskinetic effects of 3-nitropropionic acid

Abstract

Huntington's disease (HD) is a neurodegenerative disorder, with an age-related onset and a progressive development, characterized by choreiform movements. 3-Nitropropionic acid (3NP) induces the inhibition of succinate dehydrogenase (SDH), an increase in oxidative stress and anatomic changes that are related to the pathophysiology of HD. Hence, this toxin is a useful tool to study this pathology. This study compares the effects of 3NP on the development of orofacial dyskinesia (OD) and on SDH activity in young and old mice. Treatment with 3NP (5, 10, 15 or 20 mg/kg once a day, for four days) induced OD in young mice. Old mice presented an increase in the basal level of orofacial movement that was not potentiated by any dose of 3NP. Histochemical analyses showed that old mice presented an increase in the SDH activity. Finally, 3NP induced a decrease in SDH activity at both ages. We suggest that the 3NP-induced OD in young mice is related to the inhibition of SDH activity. In parallel, an enhancement in the basal activity of SDH could be related to the absence of a further increase in the OD presented by old mice treated with 3NP.