PROTEIN ALTERATIONS IN
THE POSTMORTEM FRONTAL LOBES
OF INDIVIDUALS WITH SEVERE PSYCHIATRIC DISORDERS
N. Johnston *, L.
Anderson, N. Anderson, a. Shore, R. Yolken and E.F. Torrey
Johns Hopkins University, Stanley Division of Developmental
Neurovirology, Baltimore MD
Two-dimensional gel electrophoresis is an
objective means to compare the levels of individual proteins in
different samples. We analyzed 89 postmortem frontal cortex brain
regions from individuals with schizophrenia, bipolar disorder,
major depression and unaffected normal controls. Proteins were
separated between 10-200kD and pl of 4-7, stained with Coomassie
blue, matched between gels and quantified. We used a multivariate
analysis to identify changes specific to psychiatric disease. Of
the 217 matched spots, 6 spots were decreased and 2 were
increased in level in one or more illnesses. Four of those which
were decreased were variants of glial fibrilary acidic protein
(GFAP). Ubiquinone cytochrome c reductase complex protein 1 was
reduced in depression, and dihydropyrimidinase related protein 2
was reduced in all three illnesses. Carbonic anhydrase 1 was
elevated in depressed individuals and a second as yet
unidentified protein was elevated in all three diseases.
The GFAP proteins formed a family of spots
that likely include modified and unmodified forms of this
protein. It is noted that two forms were significantly decreased
in all disorders while the other two were only altered in
non-psychotic depression. The pattern of change was distinct
between the three diseases and could not be attributed to any
known confounding variables. Two dimensional gel electrophoresis
offers a sensitive and viable means to measure changes in levels
and modifications that would not be detected by one-dimensional
electrophoresis or analysis of the corresponding nucleic acids.