Oxidative stress caused by ozone exposure induces β-amyloid 1-42 overproduction and mitochondrial accumulation by...

Oxidative stress is a major risk factor for Alzheimer's disease (AD) that has been suggested to be the trigger of AD pathology. However, whether oxidative damage precedes and contributes directly to the intracellular accumulation of beta amyloid 1-42 (βA42) peptide remains a matter of debate. Chronic exposure to low doses of ozone similar to the levels during a day of high pollution in México City causes a state of oxidative stress that elicits progressive neurodegeneration in the hippocampi of rats. Several reports have demonstrated that the mitochondria are among the first organelles to be affected by oxidative stress and βA42 toxicity and act as sites of the accumulation of βA42, which affects energy metabolism. However, the mechanisms related to the neurodegeneration process and organelle damage that occur in conditions of chronic exposure to low doses of ozone have not been demonstrated. To analyze the effect of chronic ozone chronic exposure on changes in the production and accumulation of the βA42 and βA40 peptides in the mitochondria of hippocampal neurons of rats exposed to ozone, we examined the mitochondrial expression levels of Presenilins 1 and 2 and ADAM10 to detect changes related to the oxidative stress caused by low doses of ozone (0.25ppm). The results revealed significant accumulations of βA42 peptide in the mitochondrial fractions on days 60 and 90 of ozone exposure along with reductions in beta amyloid 1-40 accumulation, significant overexpressions of Pres2 and significant reductions in ADAM10 expression. Beta amyloid immunodetection revealed that there were some intracellular deposits of βA42 and that βA42 and the mitochondrial markers OPA1 and COX1 colocalized. These results indicate that the time of exposure to ozone and the accumulation of βA42 in the mitochondria of the hippocampal cells of rats were correlated. Our results suggest that the accumulation of the βA42 peptide may promote mitochondrial dysfunction due to its accumulation and overproduction.