GSK-3 parameters in postmortem frontal cortex and hippocampus of schizophrenic patients.
The protein kinase glycogen synthase kinase-3 (GSK-3) is highly abundant in brain and involved in signal transduction cascades, particularly during neurodevelopment. We have previously found reduced GSK-3beta mRNA levels, protein levels and GSK-3 total (alpha+beta isoforms) activity in postmortem frontal cortex of schizophrenic patients in the Stanley Medical Research Institute's Brain Collection. To verify and extend these findings, GSK-3 parameters were now measured in the frontal cortex (BA9) and hippocampus obtained from the Rebecca L. Cooper Research Laboratories postmortem brain collection. Fifteen pairs of schizophrenic patients and matched control subjects have been studied. No significant differences in GSK-3alpha and GSK-3beta mRNA levels, GSK-3beta protein levels or total GSK-3 (alpha+beta) activity were found in the frontal cortex of the two diagnostic groups. Hippocampal GSK-3alpha and GSK-3beta mRNA levels were significantly lower (22% and 28%, respectively) in the tissue from the schizophrenic patients compared with the normal controls. Hippocampal GSK-3beta protein levels in the schizophrenic patients were 24% significantly lower than control values only after omission of three outlier subjects. Hippocampal total GSK-3 (alpha+beta) activity in the patients was 31% lower in the schizophrenic patients vs. control subjects. This difference was marginally significant. While our previous data on GSK-3beta in postmortem brain and the recent report that there is impaired AKT1-GSK-3beta signaling in schizophrenia suggest that changes in pathways involving protein kinases such as AKT1 and GSK-3beta in schizophrenia are complex, our present data do not provide strong evidence in support of the involvement of GSK-3beta in schizophrenia. Therefore, further investigation in a greater number of brain samples is warranted to better clarify the possible role of this enzyme in the pathophysiology of schizophrenia.
Nadri
Carmit
C
Stanley Research Center and Zlotowski Center for Neuroscience, Faculty of Health Science, Ben-Gurion University of the Negev, and Mental Health Center, Beersheva, Israel.
Dean
Brian
B
Scarr
Elizabeth
E
Agam
Galila
G
D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005625:Frontal Lobe / Q000201:enzymology* / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
D012333:RNA, Messenger; D038362:Glycogen Synthase Kinase 3