Specific subcellular changes in oxidative stress in prefrontal cortex from patients with bipolar disorder

• DOI: 10.1111/jnc.12316
• Publication Date: 2013-05-20T17:54:15Z
• Authors: Ana C. Andreazza; Jun‐Feng Wang; Faraz Salmasi; Li Shao; Lionel T. Young
• Keywords: Male; Glutathione Peroxidase; Bipolar Disorder; Electron Transport Complex I; Superoxide Dismutase; Prefrontal Cortex; Middle Aged; Mitochondria; Electron Transport Complex III; Oxidative Stress; 03 medical and health sciences; Glutathione Peroxidase GPX1; 0302 clinical medicine; Case-Control Studies; Schizophrenia; Humans; Tyrosine; Female; Lipid Peroxidation; Oxidation-Reduction; Synaptosomes

AbstractPreviously, we found decreased mitochondrial complex I subunits levels and increased protein oxidation and nitration in postmortem prefrontal cortex (PFC) from patients with bipolar disorder (BD) and schizophrenia (SCZ). The objectives of this study were to replicate our findings in an independent sample of subjects with BD, and to examine more specifically oxidative and nitrosative damage to mitochondrial and synaptosomal proteins and lipid peroxidation in myelin. We isolated mitochondria, synaptosomes, and myelin using a percoll gradient from postmortem PFC from patients with BD, SCZ, and healthy controls. Levels of mitochondrial complex I and III proteins, protein oxidation (carbonylation), and nitration (3‐nitrotyrosine) were assessed using immunobloting analysis. Lipid peroxidation [lipid hydroperoxides (LPH), 8‐isoprostane (8‐Iso), 4‐hydroxy‐2‐nonenal (4‐HNE)] were measured using colorimetric or ELISA assays. We found decreased complex I subunits levels in BD subjects compared with control (CTL), but no difference in complex III subunits. Carbonylation was increased in synaptosomes from BD group while 3‐nitrotyrosine was increased in mitochondria from BD and SCZ groups. 8‐Iso was found increased in the BD group while 4‐HNE was increased in both SCZ and BD when compared with controls with no differences in LPH. Our results suggest that in BD mitochondrial proteins are more susceptible to potentially reversible nitrosative damage while more longstanding oxidative damage occurs to synaptic proteins. image Oxidative stress has been shown to be higher in the brain of patients with bipolar disorder (BD). Here, we demonstrated increased levels of protein oxidation in synaptosomes from postmortem prefrontal cortex from patients from BD group, while 3‐nitrotyrosine was increased in mitochondria from BD and schizophrenia (SCZ) groups. Moreover, lipid peroxidation was found increased in the BD when compared with controls; suggesting that in BD mitochondrial proteins are more susceptible to potentially reversible nitrosative damage while more longstanding oxidative damage occurs to synaptic proteins.