Attentional performance, impulsivity, and related neurotransmitter systems in apoE2, apoE3, and apoE4 female transgenic mice.
BACKGROUND
The apolipoprotein E (apoE) genotype influences cognitive performance in humans depending on age and sex. While the detrimental role of the apoE4 isoform on spatial learning and memory has been well-established in humans and rodents, less is known on its impact on the executive functions.


OBJECTIVE
We aimed to evaluate the effect of apoE isoforms (apoE2, apoE3, apoE4) on visuospatial attention and inhibitory control performance in female transgenic mice, and to determine the neurochemical and neuropharmacological basis of this potential relationship.


METHODS
Female mice carrying apoE2, apoE3, and apoE4 were trained in the five-choice serial reaction time task (5-CSRTT). Upon a stable performance, we manipulated the inter-trial interval and the stimulus duration to elicit impulsive responding and engage attention respectively. We further performed a pharmacological challenge by administering cholinergic and GABAergic agents. Finally, we analyzed the levels of brain amino acids and monoamines by using reversed phase high-performance liquid chromatography (HPLC).


RESULTS
ApoE4 mice showed a deficient inhibitory control as revealed by increased perseveration and premature responding. When attention was challenged, apoE4 mice also showed a higher drop in accuracy. The adverse effect of scopolamine on the task was attenuated in apoE4 mice compared to apoE2 and apoE3. Furthermore, apoE4 mice showed less dopamine in the frontal cortex than apoE2 mice.


CONCLUSIONS
We confirmed that the apoE genotype influences attention and inhibitory control in female transgenic mice. The influence of apoE isoforms in the brain neuromodulatory system may explain the cognitive and behavioral differences attributable to the genotype.
Ingrid
I
Reverte
Fiona
F
Peris-Sampedro
Pia
P
Basaure
Leticia
L
Campa
Cristina
C
Suñol
Margarita
M
Moreno
José Luis
JL
Domingo
Maria Teresa
MT
Colomina
D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics*; D053318:Apolipoprotein E3 / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D018678:Cholinergic Agents / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D056344:Executive Function; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D006801:Humans; D007175:Impulsive Behavior; D007266:Inhibition, Psychological; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000235:genetics; D013028:Space Perception
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D018678:Cholinergic Agents; D018682:GABA Agents; D018377:Neurotransmitter Agents; D004298:Dopamine