Paradoxical effects of 137Cs irradiation on pharmacological stimulation of reactive oxygen species in hippocampal slices from apoE2 and apoE4 mice

Abstract

In humans, apoE, which plays a role in repair, is expressed in three isoforms: E2, E3, and E4. E4 is a risk factor for age-related cognitive decline (ACD) and Alzheimer's disease (AD), particularly in women. In contrast, E2 is a protective factor for ACD and AD. E2 and E4 might also differ in their response to cranial 137Cs irradiation, a form of radiation typically used in a clinical setting for the treatment of cancer. This might be mediated by reactive oxygen species (ROS) in an-apoE isoform-dependent fashion. E2 and E4 female mice received sham-irradiation or cranial irradiation at 8 weeks of age and a standard mouse chow or a diet supplemented with the antioxidant alpha-lipoic acid (ALA) starting at 6 weeks of age. Behavioral and cognitive performance of the mice were assessed 12 weeks later. Subsequently, the generation of ROS in hippocampal slices was analyzed. Compared to sham-irradiated E4 mice, irradiated E4 mice showed enhanced spatial memory in the water maze. This was associated with increased hippocampal PMA-induction of ROS. Similar effects were not seen in E2 mice. Irradiation increased endogenous hippocampal ROS levels in E2 mice while decreasing those in E4 mice. NADPH activity and MnSOD levels were higher in sham-irradiated E2 than E4 mice. Irradiation increased NADPH activity and MnSOD levels in hemi brains of E4 mice but not in those of E2 mice. ALA did not affect behavioral and cognitive performance or hippocampal formation of ROS in either genotype. Thus, apoE isoforms modulate the radiation response.

Association of Physical Activity and APOE Genotype With Longitudinal Cognitive Change in Early Parkinson Disease

“…1 However, emerging data have shown that the APOE e4 allele increases neurodegeneration mediated by tau 40 and α-synuclein [4][5][6] protein and promotes neuroinflammation 41 and oxidative stress. [42][43][44] Furthermore, the APOE e4 allele has reduced efficiency in brain homeostatic pathways, including lipid transport, glucose metabolism, and cerebrovascular function. 1 Such amyloid-unrelated effects may also negatively influence cognition in patients with PD, although this possibility requires further assessment and validation.…”

Protective Potentials of Alpha-Lipoic Acid against Ionizing Radiation-Induced Brain Damage in Rats

“…The brain is vulnerable to oxidative damage because of its high oxygen consumption and relatively low levels of antioxidants [35]. Moreover, the high concentration of unsaturated fatty acids in the brain makes this tissue a proper substrate for the occurrence of peroxidation reactions [22,36].…”