mortality/aging
• mice show increased mortality following PTZ-induced seizures with 3 of 15 mice dying
|
• 26% embryonic mortality rate
• surviving offspring exhibit a smaller population of males than females
|
growth/size/body
• P3-P14 mice exhibit lower body weight
|
• mice show reduced weight gain starting around P6 to P14
|
• perimeter and vertical axis lengths of fetuses at E16.5 are shorter resulting in small fetal size
|
behavior/neurological
• mice show increased susceptibility to pentylenetetrazole (PTZ)-induced seizures, showing severe seizures with continuous rearing and falling compared to wild-type controls that just show immobilization, with a higher cumulative seizure score and maximum seizure state
• mice exhibit epileptic patterns in EEG recordings following PTZ injection, showing a spike-wave pattern and the total time-frequency analyses suggest that neurons fire twice after PTZ injection
• mice intraperitoneally injected with NAD rescues the PTZ-induced seizure
|
• in the fear conditioning test, mice exhibit less freezing time on both day 1 and day 7 after foot-shock stimulation, indicating impaired learning and memory
|
• in the novel object recognition test, mice spend the same time with all objects and in locations, indicating no changes in the discrimination indexes between training sessions and probe test for either the object location task or the novel object recognition task, indicating impaired learning and memory
|
• in the novel object recognition test, mice spend the same time with all objects and in locations, indicating no changes in the discrimination indexes between training sessions and probe test for either the object location task or the novel object recognition task, indicating impaired learning and memory
|
• mice prefer to stay to the edges rather than explore the center area in the open field test, with both the in-zone frequency and time spent in the central zone being reduced
• in the elevated plus maze, mice spend less time on the open arm and enter the open arm fewer times
• however, no differences are seen in the total distance traveled in the open field test
• mice intraperitoneally injected with nicotinamide adenine dinucleotide (NAD) show inhibition of anxiety-like behaviors in the open field test
|
• mice prefer to stay to the edges rather than explore the center area in the open field test
|
• mice exhibit global developmental delay, especially in surface righting, auditory response to sound, in the open field, and in air righting
|
nervous system
• mice show increased susceptibility to pentylenetetrazole (PTZ)-induced seizures, showing severe seizures with continuous rearing and falling compared to wild-type controls that just show immobilization, with a higher cumulative seizure score and maximum seizure state
• mice exhibit epileptic patterns in EEG recordings following PTZ injection, showing a spike-wave pattern and the total time-frequency analyses suggest that neurons fire twice after PTZ injection
• mice intraperitoneally injected with NAD rescues the PTZ-induced seizure
|
• hippocampus area is smaller, with reduced hippocampal cell density
|
• hippocampal CA3 pyramidal neurons grown ex vivo show a hyper-branched (increased dendritic branches) phenotype
• treatment of hippocampal neurons with the PARP1 inhibitor, 1,5-dihydroxyisoquinoline (DHIQ) and TrkB-specific inhibitor, ANA-12 rescues the hyper-branched phenotype
|
• primary hippocampal neurons exhibit a higher intracellular chloride concentration
• treatment with NAD or ANA-12 rescues the increased intracellular chloride concentration
|
homeostasis/metabolism
• mice show increased mortality following PTZ-induced seizures with 3 of 15 mice dying
|