Analysis Tools
cellular
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• mice show impaired mitochondrial function in the brain
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• brain cortical mitochondria show an age-dependent decrease in baseline OCR (state 2) and maximal respiration (state 3, capacity to metabolize oxygen in the presence of ADP), while state 3 uncoupled OCR (state 3u after addition of FCCP) is significantly impaired
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• brain cortical mitochondria from 19-month-old mice show a significant decrease in the complex IV/complex II ratio and ATP levels
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• brain cortical mitochondria from both mature (9-month-old) and aged (19-month-old) mice show a significant decrease in total oxygen consumption rate (OCR) relative to mitochondria from age-matched wild-type controls
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• brain cortical mitochondria from 19-month-old mice show a significant increase in the amount of mitochondrial reactive oxygen species (mtROS)
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behavior/neurological
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• mice are viable, born at expected frequencies, and grossly normal with no overt signs of disease or altered spontaneous activity; swim speed in the water-maze, performance on the rotarod, grip test, hot plate test, and acoustic startle appear largely unaffected by age
• hippocampus-dependent burrowing and nesting behaviors are normal
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• mice exhibit age-dependent and stress-induced behavioral alterations, such as impaired learning and memory in the water-maze place navigation tests
• however, cognitive performance is normal under non-aversive conditions
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• in a large open field, mice show a significant reduction in rearing activity (a measure of exploratory drive) at all tested ages, with 9-month-old mice already resembling aged (19-month-old) mice; % of area explored is significantly lower at 9 months, but not at 14 or 19 months, of age
• 9-month-old mice show significantly reduced exploratory corner visits during the dark phase of the free adaptation stage in IntelliCage
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• in the water-maze place navigation task, mice exhibit reduced performance during acquisition and reversal training already at 9 and 14 months of age
• in the place navigation task, poor escape is accompanied by an increased number of wall approaches, with 9-month-old mice earning scores similar to those of aged mice
• in the probe trial, overall preference for the trained target zone is significantly reduced at 9 and 14 months, but not at 19 months, of age
• however, performance in the T-maze spontaneous alternation test and learning in the hippocampus-dependent IntelliCage serial reversal and chaining tasks are normal
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• in a large open field, mice show a significant increase in center avoidance (average distance to center as a measure of anxiety) both at 9 and 14 months, but not at 19 months of age
• in a light-dark transition test, 9-month-old mice show a significantly lower % of time spent in the bright compartment
• in an elevated O-maze, mice show a tendency towards increased anxiety, spending slightly less time in the open arms, but this difference is not statistically significant
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hearing/vestibular/ear
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• 3 weeks after exposure to noise (2-10 kHz broadband at intensities of 108 and 110 dB), ABR thresholds are significantly increased at 12, 24 and 32 kHz, indicating increased susceptibility to noise-induced hearing damage
• moreover, mice exhibit a ceiling effect already at 108 dB, unlike controls which display a graded response to noise with increasing thresholds from 108 to 110 dB
• however, hearing is normal under non-stressed conditions, as indicated by normal baseline ABR thresholds of ~20 dB SPL
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nervous system
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• brains of 9-month-old mice show no obvious histopathology or signs of neurodegeneration
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