Analysis Tools
nervous system
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• at E16 and P0, mice exhibit normal overall structure of the cerebral cortex, with no significant differences in cortical thickness, corpus callosum and hippocampus morphology, or cortical layer organization relative to control mice
• no defects in cortical neuron migration are noted at P0; both neural stem cells and intermediate progenitor cells show norma proliferation patterns at E16; no change in the number of TUNEL+ apoptotic cells is noted in the cortex at E17.5
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• critical synaptic proteins, including NMDA receptor subunits GRIN1, GRIN2A and GRIN2B, are downregulated in the cerebral cortex of 2-month-old mice
• postsynaptic scaffold proteins DLG4 (also known as PSD95), SHANK3, and HOMER1 are downregulated in isolated synaptic fractions of the neocortex
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• E16 and P0 brain slices show abnormal Map2 and Tubb3 (also known as Tuj1) staining patterns with fragmented longitudinal stripes substantially different from control patterns
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• in vitro differentiation of dissociated E16 cortical neurons shows impaired neuronal process development, with a significant reduction in neurite length
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• Golgi-Coxstained cortical sections from P20- or 2-month-old mice show a significant reduction in apical dendrite length
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• Golgi-Coxstained apical dendrites in the cerebral cortex and hippocampus of P20- or 2-month-old mice show a significant reduction in dendritic spine density on apical dendrites
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• EM analysis of synapses in the prefrontal cortex of 2- to 4-month-old mice shows a significant reduction in both the length and thickness of the postsynaptic density
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• spontaneous glutamatergic excitatory postsynaptic currents (sEPSCs) of prefrontal cortex pyramidal neurons from P15- to P20-old mice show a significant increase in sEPSC peak amplitude
• however, no change in sEPSC amplitude is seen in prefrontal cortex slices from 4-month-old mice, suggesting that the effects on neuronal synaptic network activity may vary at different developmental stages
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• whole-cell voltage-clamp recordings of spontaneous glutamatergic excitatory postsynaptic currents (sEPSCs) show a significant decrease in sEPSC frequency of pyramidal neurons in prefrontal cortex slices from 4-month-old mice
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• sEPSCs of prefrontal cortex pyramidal neurons from P15- to P20-old mice show a significant increase in sEPSC frequency
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• average paired-pulse ratio (PPR) of evoked EPSCs is significantly increased at interpulse intervals of 25, 50, and 100 ms in prefrontal cortex pyramidal neurons from 2-month-old mice
• however, no change in average PPR is seen in pyramidal neurons from P15- to P20-old mice
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behavior/neurological
| N |
• mice show normal memory and cognition in the Morris water maze and novel object recognition test, normal instinctive behavior in a nest building test, and unaffected motor coordination/balance abilities in a balance beam test
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• in an open-field assay, mice spend less time in the central area and more time in the peripheral areas, with no significant change in total distance traveled or mean speed relative to controls
• however, in an elevated plus maze test, mice show only a small (non-significant) decrease in the percentage of time spent in the open arm
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• during stage 3 of a three-chamber test, mice show no preference for a novel stranger mouse (stranger 2), indicating impaired preference for social novelty
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• mice show increased self-grooming duration and frequency relative to controls
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• in a marble burying test, mice show increased marble burying behavior relative to control mice
• in a self-grooming test, mice show increased self-grooming duration and frequency during the 10 min free movement session
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• in a reciprocal social interactions test, 2- to 3-month-old mice spend significantly less time interacting with a newly introduced mouse than controls
• during stage 2 of a three-chamber test, mice spend more time in the empty compartment than exploring a stranger mouse (stranger 1), suggesting impaired social interaction
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