Investigating the Effects of Cortisol on Oxidative Stress Vulnerability in Human Glial Cells: Implications for PTSD and Neurodegenerative Risk
Heeseong Yang
Portsmouth Abbey School, Portsmouth, Rhode Island, USA
Publication date: November 20, 2025
Portsmouth Abbey School, Portsmouth, Rhode Island, USA
Publication date: November 20, 2025
DOI: http://doi.org/10.34614/JIYRC2025II37
ABSTRACT
Post-Traumatic Stress Disorder (PTSD) is characterized by abnormal activity of the HPA axis and thereby causes the cortisol level to fluctuate significantly. This increases the danger of neurodegeneration in the brain. However, previous studies have not yet clarified the effect of acute cortisol on the H₂O₂ tolerance of glial cells. Thus, this study aims to find out if acute cortisol pretreatment on human glial cells increases their sensitivity to oxidative stress damage. After 24 hours of 6 µM cortisol pretreatment on U-87 MG cells, 0.01 nM or 0.1 nM H₂O₂ were treated again for 24 hours. Cell viability, number of live or dead cells, and the size of cells were measured through AO/PI-based LUNA-FL. As a result, cortisol reduced the cell viability from 97.3% to 75.0% at 0.01 nM H₂O₂ and 86.6% to 67.6% at 0.1 nM H₂O₂. Additionally, cortisol decreased live-cell yield, and shrank average cell size 18.2 to 13.8 µm at 0.01 nM H₂O₂ and 14.6 to 9.1 µm at 0.1 nM H₂O₂. Ultimately, acute cortisol sensitizes glia to oxidative stress, contradicting a preconditioning hypothesis and suggesting glucocorticoid-linked suppression of antioxidant defenses. These data offer a cellular mechanism relevant to PTSD-associated neurodegenerative risk.
Post-Traumatic Stress Disorder (PTSD) is characterized by abnormal activity of the HPA axis and thereby causes the cortisol level to fluctuate significantly. This increases the danger of neurodegeneration in the brain. However, previous studies have not yet clarified the effect of acute cortisol on the H₂O₂ tolerance of glial cells. Thus, this study aims to find out if acute cortisol pretreatment on human glial cells increases their sensitivity to oxidative stress damage. After 24 hours of 6 µM cortisol pretreatment on U-87 MG cells, 0.01 nM or 0.1 nM H₂O₂ were treated again for 24 hours. Cell viability, number of live or dead cells, and the size of cells were measured through AO/PI-based LUNA-FL. As a result, cortisol reduced the cell viability from 97.3% to 75.0% at 0.01 nM H₂O₂ and 86.6% to 67.6% at 0.1 nM H₂O₂. Additionally, cortisol decreased live-cell yield, and shrank average cell size 18.2 to 13.8 µm at 0.01 nM H₂O₂ and 14.6 to 9.1 µm at 0.1 nM H₂O₂. Ultimately, acute cortisol sensitizes glia to oxidative stress, contradicting a preconditioning hypothesis and suggesting glucocorticoid-linked suppression of antioxidant defenses. These data offer a cellular mechanism relevant to PTSD-associated neurodegenerative risk.
