AN EARLY-STAGE MECHANISM OF THE AGE-ASSOCIATED MITOCHONDRIAL DYSFUNCTION IN THE BRAIN OF SAMP8 MICE - AN AGE-ASSOCIATED NEURODEGENERATION ANIMAL-MODEL

In order to characterize the early stage of mitochondrial dysfunction, we investigated the redox state and oxidative phosphorylation of the brain mitochondria from e-month-old Senescence-accelerated mouse (SAM) P8 and SAMR1 mice; SAMP8 mice exhibit various signs of age-associated neurodegeneration and rapid mitochondrial dysfunction, although SAMR1 mice do not. The redox state was estimated as the reduction rate of Cu -pyruvaldehyde-bis (N4-methylthiosemicarbazone) (Cu-PTSM), the reducti on of which is closely related to the electron leakage from the mitoch ondrial electron transport system in the brain, using electron spin re sonance spectrometry (ESRS). The oxidative phosphorylation was measure d polarographically. The SAMP8 mouse brain mitochondria demonstrated h igher redox state and a higher activity of mitochondrial respiration w ith lower respiration control ratio than the mitochondria of SAMR1 mou se brains. This indicates that an inefficient hyperactive state can ex ist in the mitochondrial electron transport system before the age-asso ciated mitochondrial dysfunction develops. (C) 1998 Elsevier Science i reland Ltd. All rights reserved.