Oxidation and nitration in dopaminergic areas of the prefrontal cortex from patients with bipolar disorder and schizophrenia.
BACKGROUND
Increased oxidative stress is strongly implicated in bipolar disorder (BD), where protein oxidation, lipid peroxidation and oxidative damage to DNA have been consistently reported. High levels of dopamine (DA) in mania are also well-recognized in patients with BD, and DA produces reactive oxygen species and electron-deficient quinones that can oxidize proteins when it is metabolized.


METHODS
Using immunohistochemistry and acceptor photobleaching Förster resonance energy transfer (FRET), we examined oxidation and nitration of areas immunoreactive for the DA transporter (DAT) and tyrosine hydroxylase (TH) in the postmortem prefrontal cortex from patients with BD, schizophrenia and major depression as well as nonpsychiatric controls.


RESULTS
We found increased oxidation of DAT-immunoreactive regions in patients with BD (F3,48 = 6.76, p = 0.001; Dunnett post hoc test p = 0.001) and decreased nitration of TH-immunoreactive regions in both patients with BD (F3,45 = 3.10, p = 0.036; Dunnett post hoc test p = 0.011) and schizophrenia (p = 0.027). On the other hand, we found increased global levels of oxidation in patients with BD (F3,44 = 6.74, p = 0.001; Dunnett post hoc test p = 0.001) and schizophrenia (p = 0.020), although nitration levels did not differ between the groups (F3,46 = 1.75; p = 0.17).


CONCLUSIONS
Limitations of this study include the use of postmortem brain sections, which may have been affected by factors such as postmortem interval and antemortem agonal states, although demographic factors and postmortem interval were accounted for in our statistical analysis.


CONCLUSIONS
These findings suggest alterations in levels of protein oxidation and nitration in DA-rich regions of the prefrontal cortex in patients with BD and schizophrenia, but more markedly in those with BD.
Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ont., Canada.
Helena Kyunghee
HK
Kim
Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ont. and The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ont., Canada.
Ana Cristina
AC
Andreazza
Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ont., Canada.
Pok Yik
PY
Yeung
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ont., Canada.
Cameron
C
Isaacs-Trepanier
Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, Ont. and The Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ont., Canada.
L Trevor
LT
Young
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins