NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder

Abstract

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

Post-traumatic Stress Disorder: The Influence of the Environmental Context and Analysis of Oxidative Stress and Inflammatory and Glycemic Markers in Women Living in Kurdistan Regional Government-Iraq

“…The current study demonstrated that there was a depletion in the non-enzymatic antioxidant GSH concentration in PTSD women when compared to the external healthy control group. These findings are similar to those of Borovac et al and Petrovic et al, who showed GSH depletion in humans with PTSD [42] and in animal rats with PTSD [35]. Our findings suggest that, when OXS persists for an extended period and the body's cellular defense mechanisms cannot effectively combat these processes, the available free GSH decreases, resulting in irreversible cellular degeneration and cell mortality [43].…”

“…The current result is in line with other studies indicating that civilian earthquake survivors and the military population developed PTSD, which was associated with an increase in the level of MDA biomarkers of lipid peroxidation [ 12 , 33 ]. Furthermore, two animal studies have shown an association between PTSD and lipid peroxidation in rats with PTSD, showing elevated levels of MDA in various organ tissues when compared to healthy rats [ 34 , 35 ].…”

Oxidative Dysregulation in Early Life Stress and Posttraumatic Stress Disorder: A Comprehensive Review

“…Additional animal studies utilizing a SPS model of PTSD in rats, also reported (i) decreased SOD activity; (ii) increased expression of NOX-2 subunits; (iii) increased MDA and phosphorylated AMPK; (iv) decreased GSH levels in amygdala and hippocampi; (v) elevated IL-6 and IL-1beta levels; (vi) higher expression of iNOS and p-p38 in hippocampi; (vii) higher cyclooxygenase-2 (COX-2) mRNA and protein expression, TNF-α, IL-6, prostaglandin E2 (PGE2), and NO levels; and (viii) cell apoptosis in the hippocampi of stress exposed animals [118][119][120][121]. In an IFS rat model of PTSD, the stress-exposed group showed a significant up-regulation of NOX2 and 8-OH-DG levels and a down-regulation of glutamic acid GAD-67 and parvalbumin in the animals' hippocampi [122].…”

S-Ketamine Pretreatment Alleviates Anxiety-Like Behaviors and Mechanical Allodynia and Blocks the Pro-inflammatory Response in Striatum and Periaqueductal Gray From a Post-traumatic Stress Disorder Model

“…Significant decreases in IL-10 and TNF-α expression and increases in the iNOS in microglial isolated from the frontal cortex of the SPS-exposed rats on Day1, but not on Day3 or Day7 ( Cotrone et al, 2021 ). Oxidative stress is present in hippocampus and amygdala but not in cortex on Day7 after the SPS procedure ( Petrovic et al, 2018 ). SPS exposure increased the levels of pro-inflammatory markers and microglia activation in the hippocampus and PFC on Day8 ( Hong et al, 2021 ).…”