Rescue Type:
RESCUE-Pharmaceutical
Rescue Paradigm:
4EGI-1, an inhibitor of eIF4E/eIF4G interactions was used to block the synaptic and behavioral consequences of increased eIF4E expression in transgenic mice over-expressing EIF4E. 4EGI-1 dissolved in 100% DMSO was diluted in vehicle [0.5% (2- hydroxypropyl)--cyclodextrin and 1% DMSO in ACSF]. 4EGI-1 (20 M) or vehicle were infused over 1 min (0.5 L/min; Harvard Apparatus) in anesthetized mice through implanted cannulae.
Treatment does not improve measured phenotype (was expected to do so)
Ameliorated
Treatment provides partial correction or improvement of measured phenotype
No adverse effect
Treatment does not affect the parameter adversely
Sustained effect
Treatment has long term effect of restoration or amelioration, tested AFTER stopping administration (not applied for continuing long-term treatment) . Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
No sustained effect
Treatment has no long term of restoration or amelioration detectable, after stopping administration. Will be applied only where treatment has had restorative effects during administration or in the first battery of tests conducted.
Description: Transgenic mice treated with 4egi-1 exhibited a decrease in repetitive behavior during the marble burying task, which started on day four and persisted throughout day five
Exp Paradigm: Sample size is 22 mice. males only.
Description: 4egi-1 rescued the social behavior deficits displayed by the eif4e transgenic mice in the three-chamber test, as they exhibited an increased interaction with a freely moving stranger mouse
Exp Paradigm: Reciprocal social interaction test. males only.
Description: 4egi-1 rescued the social behavior deficits displayed by the eif4e transgenic mice in the three-chamber test, as they exhibited an increased preference for a non-specific stranger compared to a novel object
Exp Paradigm: Reciprocal social interaction test. males only.
Description: Transgenic mice treated with 4egi-1 exhibited improved performance in the reversal phase of the y-maze test compared to untreated eif4e transgenic mice
Exp Paradigm: Water y-maze; morris water maze test. males only.- morris water maze test
Description: Transgenic mice treated with 4egi-1 exhibited improved performance in the reversal phase of the y-maze test compared to untreated eif4e transgenic mice
Exp Paradigm: Water y-maze; morris water maze test. males only.-water y-maze
Description: Transgenic mice treated with 4egi-1 exhibited reduced puromycin-labeling of newly synthesized proteins, compared to untreated eif4e transgenic mice
Exp Paradigm: Puromycin was infused into the lateral ventricle of cannulated mice and newly synthesized proteins were labelled using sunset and de novo cap-dependent translation was observed. males only.
Description: Transgenic mice treated with 4egi-1 exhibited reduced binding of eif4e to eif4g in the brain, compared to untreated eif4e transgenic mice
Exp Paradigm: Transgenic brain tissue was used as sample. males only.
Description: Eif4e transgenic mice show slight increase in total time spent moving and total distance travelled compared to controls Exp Paradigm: Males only
Description: Eif4e transgenic mice show slight increase in total time spent moving and total distance travelled compared to controls Exp Paradigm: Males only
Description: Eif4e transgenic mice show increased dendritic spine density and a smaller spine volume compared to controls Exp Paradigm: Dendritic spines were imaged using two-photon laser-scanning microscopy. males only.
Spontaneous post synaptic event frequency: excitatory currents1
Increased
Description: Eif4e transgenic mice show an increase in the frequency but not amplitude of spontaneous synaptic excitatory mepsc events in layers ii/iii of acute mpfc slices, compared to controls. no changes were observed in layer v. Exp Paradigm: Males only
Spontaneous post synaptic event amplitude: inhibitory currents1
Increased
Description: Eif4e transgenic mice show an increase in the amplitude, but not frequency, of inhibitory mipsc events in layers ii/iii of acute mpfc slices, compared to controls. no changes were observed in layer v. Exp Paradigm: Males only
Description: Eif4e transgenic mice show preference for a novel inanimate object over a stranger mouse, compared to controls Exp Paradigm: Novel object interaction test. males only.
Description: Eif4e transgenic mice show reduced preference for a novel stranger compared to a novel inanimate object, compared to controls Exp Paradigm: Males only.
Description: Eif4e transgenic mice exhibited cognitive inflexibility in being impaired in locating the new platform positions compared to control mice Exp Paradigm: Males only- morris water maze test
Description: Eif4e transgenic mice did not exhibit a significant reduction in freezing responses following extinction training as did control mice Exp Paradigm: Males only
Description: Eif4e transgenic mice exhibited cognitive inflexibility in being impaired in locating the new platform positions compared to control mice Exp Paradigm: Males only-water y-maze
Description: Eif4e transgenic mice show increased de novo cap-dependent translation in the brain, compared to controls Exp Paradigm: Puromycin was infused into the lateral ventricle of cannulated mice and newly synthesized proteins were labeled using sunset and de novo cap-dependent translation was observed. males only.
Description: Eif4e transgenic mice show increased binding of eif4e to eif4g in the brain, compared to controls Exp Paradigm: Transgenic brain tissue was used as sample. males only.
Description: Eif4e transgenic mice show increased expression of eif4e in multiple brain regions including the prefrontal cortex, striatum, hippocampus and cerebral cortex, compared to controls Exp Paradigm: Males only
