Genotype differences in anxiety and fear learning and memory of WT and ApoE4 mice associated with enhanced generation of hippocampal reactive oxygen species

Abstract

Apolipoprotein E (apoE), involved in cholesterol and lipid metabolism, also influences cognitive function and injury repair. In humans, apoE is expressed in three isoforms. E4 is a risk factor for age-related cognitive decline and Alzheimer’s disease, particularly in women. E4 might also be a risk factor for developing behavioral and cognitive changes following 56Fe irradiation, a component of the space environment astronauts are exposed to during missions. These changes might be related to enhanced generation of reactive oxygen species (ROS). In this study, we compared the behavioral and cognitive performance of sham-irradiated and irradiated wild-type (WT) mice and mice expressing the human E3 or E4 isoforms, and assessed the generation of ROS in hippocampal slices from these mice. E4 mice had greater anxiety-like and conditioned fear behaviors than WT mice, and these genotype differences were associated with greater levels of ROS in E4 than WT mice. The greater generation of ROS in the hippocampus of E4 than WT mice might contribute to their higher anxiety levels and enhanced fear conditioning. In E4, but not wild-type, mice, PMA-treated hippocampal slices showed more DHE oxidation in sham-irradiated than irradiated mice and hippocampal HO-1 levels were higher in irradiated than sham-irradiated E4 mice.

Apolipoprotein E gene polymorphism, trauma burden, and posttraumatic stress symptoms in U.S. military veterans: Results from the National Health and Resilience in Veterans Study

“…Greater hippocampal atrophy and volume loss in ε4 carriers may also contribute to deficits in memory for fear extinction (den Heijer et al., ; Fanselow, ; Pievani et al, ), which can maintain re‐experiencing/intrusion symptoms. Villasana, Weber, Akinyeke, and Raber () found that mice carrying the ε4 allele had higher levels of heme oxygenase‐1, a marker of stress, in the hippocampus, and also exhibited greater anxiety‐related behaviors and conditioned fear responding. These findings suggest a possible mechanism linking ε4 carriage and intrusive symptoms among highly trauma‐exposed veterans.…”

Genetic deletion of Polo-like kinase 2 reduces alpha-synuclein serine-129 phosphorylation in presynaptic terminals but not Lewy bodies

“…Behavioral analysis was performed on 4–5 month-old animals (N= WT/PLK2 WT 11, WT/PLK2 Het 7, Syn-GFP/PLK2 WT 15, Syn-GFP/PLK2 Het 6, Syn-GFP/PLK2 KO 11 animals). Open field, novel object, rotarod, Morris water maze, contextual and cued fear conditioning behavior measures were performed as previously published ( 55 ).…”

Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy

“…The presence ApoE4 has been shown to be associated with increased oxidative stress in the brains of affected animals 19 . We evaluated the total ApoE concentration in the CSF of young males with cALD and found a mean of 17 µg/mL, consistent within the range of previously published results 20–22 (Fig.…”