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 2-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 reduction of which is closely related to the electron leakage from the mitochondrial electron transport system in the brain, using electron spin resonance spectrometry (ESRS). The oxidative phosphorylation was measured polarographically. The SAMP8 mouse brain mitochondria demonstrated higher redox state and a higher activity of mitochondrial respiration with lower respiration control ratio than the mitochondria of SAMR1 mouse brains. This indicates that an inefficient hyperactive state can exist in the mitochondrial electron transport system before the age-associated mitochondrial dysfunction develops.
Department of Neurosurgery, Faculty of Medicine, Kyoto University, Japan.
T
T
Nishikawa
J A
JA
Takahashi
Y
Y
Fujibayashi
H
H
Fujisawa
B
B
Zhu
Y
Y
Nishimura
K
K
Ohnishi
K
K
Higuchi
N
N
Hashimoto
M
M
Hosokawa
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport / Q000502:physiology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology*; D009942:Organometallic Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D013882:Thiosemicarbazones / Q000378:metabolism; D013997:Time Factors
D009942:Organometallic Compounds; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex