behavior/neurological
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• in the open field (OF) test, total distance moved is reduced by 40% and average speed is reduced by 39.6% relative to controls, whereas no differences are observed in the ratio of the distance moved in the center to the distance moved in the periphery, or in the ratio of time spent in the center to the time spent in the periphery
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bradykinesia
(
J:347870
)
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• combined behavioral analysis of 8-weeks-old male mice using the rotarod test, open field test, CatWalk analysis, and elevated plus maze (EPM) indicate a characteristic bradykinesia with a reduction in spontaneous movements
• in the open field (OF) test, total distance moved is reduced by 40% and average speed is reduced by 39.6% relative to controls, whereas no significant differences are observed in the ratio of the distance moved in the center to the distance moved in the periphery, or in the ratio of time spent in the center to the time spent in the periphery
• CatWalk analysis shows that the base of support (BOS) between the hind paws is reduced by 34.8% and BOS between the front paws is reduced by 26.1% whereas inter-paw coordination is normal, indicating decreased amplitude of stepping; all of the paw print areas show a marked decline (approximately 58.1% for the left front paw, 60.4% for the left hind paw, 54.1% for the right front paw, and 44.7% for the right hind paw), confirming bradykinesia
• in the rotarod test, no significant difference is observed in the latency to fall relative to controls, indicating absence of ataxia and normal balance ability
• in the EPM test, no significant differences are observed in the duration or frequency in the central platform, in the closed arms, and in the open arms relative controls, suggesting that emotional behavior is largely unaffected
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nervous system
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• TEM analysis of PC mitochondria shows a significant increase in mitochondrial circularity relative to controls
• however, no significant change in PC mitochondrial density, area or perimeter is observed
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• electrical patch clamp recordings on freshly isolated 4/5 lobes of the cerebellar cortex show alterations in the properties of both spontaneous and evoked firings in PCs
• analysis of spontaneous action potential (AP) firings of PCs shows that the AP half-width is reduced by 19.7% while the rise and decay slope becomes steeper by 21.8% and 21.1%, respectively, relative to controls
• analysis of the evoked spikes of PCs shows that the proportion of active and inactive PCs is reduced by 5% relative to controls (68% vs 73%, respectively)
• however, the total firing number of active and inactive PCs is not significantly altered at any given current
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cellular
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• TEM analysis of PC mitochondria shows a significant increase in mitochondrial circularity relative to controls
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• TEM analysis of PC mitochondria shows a significant increase in mitochondrial circularity relative to controls
• however, no significant change in PC mitochondrial density, area or perimeter is observed
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• microplate reader assays indicate that the mitochondrial membrane potential (MMP) level is increased by 28.86% while the ATP level is increased by 57.86% in isolated cerebellum tissue
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• reactive oxygen species (ROS) probe imaging shows that ROS generation is significantly increased in the molecular layer of cerebellar tissue
• a microplate reader assay indicates that ROS generation is increased by 27.08% in isolated cerebellum tissue
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muscle
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• 8-weeks-old male mice exhibit no hypotonia (a typical symptom of cerebellar disorders) by electromyogram recordings detection on the gastrocnemius muscle
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growth/size/body
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• 8-weeks-old male mice exhibit no significant changes in average body length, ratio of head length to body length, and average body weight relative to controls
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