TY - JOUR
T1 - Relationship between Cognitive Dysfunction and Age-Related Variability in Oxidative Markers in Isolated Mitochondria of Alzheimer’s Disease Transgenic Mouse Brains
AU - Yoshida, Naoki
AU - Kato, Yugo
AU - Takatsu, Hirokatsu
AU - Fukui, Koji
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2
Y1 - 2022/2
N2 - Many neurodegenerative disorders, including Alzheimer’s disease (AD), are strongly associated with the accumulation of oxidative damage. Transgenic animal models are commonly used to elucidate the pathogenic mechanism of AD. Beta amyloid (Aβ) and tau hyperphosphorylation are very famous hallmarks of AD and well-studied, but the relationship between mitochondrial dysfunction and the onset and progression of AD requires further elucidation. In this study we used transgenic mice (the strain name is 5xFAD) at three different ages (3, 6, and 20 months old) as an AD model. Cognitive impairment in AD mice occurred in an age-dependent manner. Aβ1-40 expression significantly increased in an age-dependent manner in all brain regions with or without AD, and Aβ1-42 expression in the hippocampus increased at a young age. In a Western blot analysis using isolated mitochondria from three brain regions (cerebral cortex, cerebellum, and hippocampus), NMNAT-3 expression in the hippocampi of aged AD mice was significantly lower than that of young AD mice. SOD-2 expression in the hippocampi of AD mice was lower than for the age-matched controls. However, 3-NT expression in the hippocampi of AD mice was higher than for the age-matched controls. NQO-1 expression in the cerebral cortex of AD mice was higher than for the age-matched controls at every age that we examined. However, hippocampal NQO-1 expression in 6-month-old AD mice was significantly lower than in 3-month-old AD mice. These results indicate that oxidative stress in the hippocampi of AD mice is high compared to other brain regions and may induce mitochondrial dysfunction via oxidative damage. Protection of mitochondria from oxidative damage may be important to maintain cognitive function.
AB - Many neurodegenerative disorders, including Alzheimer’s disease (AD), are strongly associated with the accumulation of oxidative damage. Transgenic animal models are commonly used to elucidate the pathogenic mechanism of AD. Beta amyloid (Aβ) and tau hyperphosphorylation are very famous hallmarks of AD and well-studied, but the relationship between mitochondrial dysfunction and the onset and progression of AD requires further elucidation. In this study we used transgenic mice (the strain name is 5xFAD) at three different ages (3, 6, and 20 months old) as an AD model. Cognitive impairment in AD mice occurred in an age-dependent manner. Aβ1-40 expression significantly increased in an age-dependent manner in all brain regions with or without AD, and Aβ1-42 expression in the hippocampus increased at a young age. In a Western blot analysis using isolated mitochondria from three brain regions (cerebral cortex, cerebellum, and hippocampus), NMNAT-3 expression in the hippocampi of aged AD mice was significantly lower than that of young AD mice. SOD-2 expression in the hippocampi of AD mice was lower than for the age-matched controls. However, 3-NT expression in the hippocampi of AD mice was higher than for the age-matched controls. NQO-1 expression in the cerebral cortex of AD mice was higher than for the age-matched controls at every age that we examined. However, hippocampal NQO-1 expression in 6-month-old AD mice was significantly lower than in 3-month-old AD mice. These results indicate that oxidative stress in the hippocampi of AD mice is high compared to other brain regions and may induce mitochondrial dysfunction via oxidative damage. Protection of mitochondria from oxidative damage may be important to maintain cognitive function.
KW - Alzheimer’s disease
KW - Cognitive impairment
KW - Mi-tochondria
KW - Oxidative stress
KW - Reactive oxygen species
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U2 - 10.3390/biomedicines10020281
DO - 10.3390/biomedicines10020281
M3 - Article
AN - SCOPUS:85123607694
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 2
M1 - 281
ER -