EFFECT OF A UBIQUINONE-LIKE MOLECULE ON OXIDATIVE ENERGY-METABOLISM IN RAT CORTICAL SYNAPTOSOMES AT DIFFERENT AGES

Persistent stimulation of energy consumption, induced by depolarizatio n with veratridine, mimics a condition of abnormally enhanced energy d emand and causes an increase in the oxygen consumption rate (QO(2)) an d in the interconversion of pyruvate dehydrogenase complex (PDHc) into its active form. Wistar rats at the age of 26 months do not show alte rations of QO(2) and of the ability of veratridine to increase QO(2) i n compar;son with 6 month-old animals whereas the active form of PDHc is slightly but significantly reduced. Idebenone, a ubiquinone-like mo lecule (1 mu M), does not affect the QO(2) or PDHc activation state in resting conditions but attenuates the veratridine-challenged increase in QO(2) at all the ages tested and attenuates the increase in the pe rcentage of PDHa reaching statistical significance in 26-month-old rat s. At higher concentration (10 mu M) idebenone totally abolishes the v eratridine-induced increase in PDHa also in the 6 month-old rats. At t he lower concentration, the drug does not affect the increase in QO(2) induced by an uncoupler of oxidative phosphorylation. The results obt ained suggest a protective effect of idebenone on the cerebral tissue against stressful conditions; this action may be exerted at the level of some mitochondrial component and/or on the Na+ homeostasis.