behavior/neurological
N |
• mice exhibit normal learning and memory functions in Morris water maze testing
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• in the hole-board test, both mean total distance traveled and mean number of head pokes into holes are significantly less than in wild-type controls
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• in the elevated zero-maze test, mice spend significantly more mean time in the closed arms and less mean time in the open arms; mean frequency of open-arm entries and mean distance traveled in the open arms are significantly less than those in wild-type controls
• in the open-field test, both mean total distance traveled and mean time spent in the center of the chamber are significantly less than in wild-type controls
• in the hole-board test, both mean total distance traveled and mean number of head pokes into holes are significantly less than in wild-type controls
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• in the horizontal balance-beam test, mice spend a significantly longer time than wild-type cross to cross the beam, as the width of the balance beam is reduced
• in the accelerating-rotarod test, the mean latency time that mice stay on the rotarod as it accelerates is significantly shorter than that in wild-type controls
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• in the cylinder test, the mean number of spontaneous rears is significantly less than in wild-type controls
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nervous system
• Iba1 immunostaining revealed dense hypertrophic microglia in hippocampal sections, unlike the ramified resting microglia observed in wild-type controls
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• microglia are hypertrophic, increased in number and stain more intensely with Iba1 antibody, suggesting microglial cell activation in the hippocampus
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• Golgi-Cox staining revealed a significant reduction in dendritic spine density on pyramidal cells in hippocampal CA regions
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• Bielschowsky silver staining revealed abnormal "hairy" basket cells surrounding Purkinje cell soma in the cerebellum, not observed in wild-type controls
• however, no loss in cerebellar Purkinje cell number is observed
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• Olig2+ cell percentage is reduced in the cerebral cortex region relative to that in wild-type controls
• however, Olig2+ cell percentage is normal in the corpus callosum region
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• Golgi-Cox staining revealed a significant reduction in dendritic spine density on pyramidal cells in hippocampal cornu ammonis (CA) regions
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• co-localization analysis of excitatory synaptic marker, vesicular glutamate transporter 1 (VGlut1) and C1q shows a 1.6-fold increase of double-positive synapses in hippocampal sections
• however, total VGlut1 protein level in the hippocampus is normal
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• co-localization analysis of inhibitory synaptic marker vesicular GABA transporter (VGAT) and C1q shows a 2.5-fold increase of double-positive synapses in hippocampal sections
• VGAT levels are reduced by ~20% in the hippocampus
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• Western blot analysis of myelin basic protein (MBP) isoforms (21, 18, 17, and 14 kD) in cerebral cortex lysates revealed a marginal increase in MBP expression
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immune system
• Iba1 immunostaining revealed dense hypertrophic microglia in hippocampal sections, unlike the ramified resting microglia observed in wild-type controls
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• microglia are hypertrophic, increased in number and stain more intensely with Iba1 antibody, suggesting microglial cell activation in the hippocampus
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• mice show a 1.5-fold increase in complement component C1q fluorescence intensity in hippocampal sections and a 1.7-fold increase of constituent C1q expression in the cerebellum; however, C1q mRNA levels in the hippocampus and cerebellum are not significantly altered
• complement C3 levels in hippocampal extracts are normal
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hematopoietic system
• Iba1 immunostaining revealed dense hypertrophic microglia in hippocampal sections, unlike the ramified resting microglia observed in wild-type controls
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• microglia are hypertrophic, increased in number and stain more intensely with Iba1 antibody, suggesting microglial cell activation in the hippocampus
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homeostasis/metabolism
• mice show a 1.5-fold increase in complement component C1q fluorescence intensity in hippocampal sections and a 1.7-fold increase of constituent C1q expression in the cerebellum; however, C1q mRNA levels in the hippocampus and cerebellum are not significantly altered
• complement C3 levels in hippocampal extracts are normal
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