Age- and sex-dependent effects of single prolonged stress on behavioral, hematological, and oxidative stress parameters in C57BL/6J mice

Post-traumatic stress disorder (PTSD) is a pathological condition associated with the experience of traumatic stress. This study investigated the age- and sex-specific effects of single prolonged stress (SPS), a validated rodent PTSD model, on behavioral, hematological, and oxidative stress parameters in C57BL/6J mice. Young adult (∼2.5 months) and middle-aged (10-12 months) male and female mice were subjected to SPS that included restraint, forced swimming, predator sound exposure, and ether anesthesia. Young adult SPS-treated males and females exhibited anxiety-related behavior in the open field test, which was accompanied by an elevated blood leukocyte count. Additionally, young SPS-treated males had lipid peroxidation in the diencephalon-midbrain region. Young adult females subjected to SPS showed impairment of spatial memory in the T-maze, higher hemoglobin levels, and lower plasma paraoxonase activity. In middle-aged males and females, SPS led to lower blood leukocyte levels. In addition, middle-aged SPS males showed impaired spatial memory, higher plasma protein levels, lower blood glucose, and lower NAD(P)H:quinone oxidoreductase 1 (NQO1) activity in the cerebral cortex. In middle-aged females, SPS exposure led to lower hemoglobin levels, higher plasma myeloperoxidase activity, and elevated plasma glucose levels. Age-related shifts were also evident in control mice, with older animals showing elevated baseline leukocyte counts, anxiety-like behavior, and decreased antioxidant defenses (NQO1 and glutathione-S-transferase, only in females) and higher lipid peroxides (only in males) in the diencephalon-midbrain compared to young adult ones. Overall, our results suggest that SPS induces age- and sex-dependent alterations.