Analysis Tools
behavior/neurological
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• mutants exhibit enhanced performance on day 3 and 4 of rotarod testing at 6 months of age but no differences are seen at 12 months
• however, mice do not exhibit differences in emotional behaviors or in tests associated with learning
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• in the first segment of the open field assessment (0-300 seconds), mutants make more entries into the center zone compared to wild-type mice, spend more time in the center and exhibit more frequent freezing bouts and increased amount of time spent freezing
• however, no differences are seen in the second and last segments of the open field assessment
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• in the open field assessment, total distance traveled is slightly increased in 6 month old mutants but is not different at 12 months of age
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cellular
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• mitochondria in the striatum of 23 month old mutants are about 10% longer
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• by 23 months of age, mitochondria exhibit crista swelling, disorganization and severely condensed mitochondria
• mitochondria with disorganized cristae is seen in the hippocampus and cortex, with the cortex more affected than the hippocampus
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• mitochondria in the striatum of 15 month old mice have abnormal shape that resembles beads-on-the-string
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• the number of mitochondria per neuropil length in the striatum is reduced in 23 month old mutants
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• increase in the number of swollen mitochondria with altered cristae in the striatum of 15 month old mice
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• mitochondrial defects consistent with mitochondrial fission arrest
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homeostasis/metabolism
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• the average DOPAC/dopamine and homovanillic acid /dopamine ratios at baseline are almost double compared to wild-type ratios
• however, the average level of extracellular metabolites homovanillic acid and DOPAC remains similar to wild-type mice
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• cortical and hippocampal regions have a higher abundance of lipid droplets and lipofuscin accumulation
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nervous system
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• in some brain regions of the oldest mutants, tau CP-13 pSer202 immunoreactivity is increased, with some positive puncta, increased neuropil immunoreactivity, cytoplasmic staining, and occasional positive neurites which are not seen in wild-type mice
• the corpus callosum shows heavier tau staining and slightly increased cortical tau
• tau immunostaining in the posterior amygdaloid nucleus
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• mice do not show a decline in the homovanillic acid/dopamine ratio from 6 to 18 months of age as is seen in wild-type mice, suggesting that the sum of dopamine metabolism and release is altered
• basal dopamine and amphetamine-stimulated extracellular release of dopamine is decreased in the striatum at 12, but not 6, months of age
• exocytotic release of dopamine and its metabolites from the vesicular pool is impaired
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cardiovascular system
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• heart appears normal
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renal/urinary system
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• kidneys appear normal
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respiratory system
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• lungs appear normal
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