POSTER
ANALIZING EXPRESSION
PROFILES OF VALPROATE REGULATED GENES AND GENES INVOLVED IN BIPOLAR DISORDER
J.F.
Wang, L. Shao, X.J. Sun, and L. T. Young. Department of Psychiatry, University
of Toronto, Canada
DNA
microarray technology was used to analyze gene expression profiles after chronic
treatment with the mood stabilizing drug Valproate at a therapeutically relevant
concentration in primary cultured rat cerebral cortical cells. The microarray
used contained approximately 7,000 full-length sequences and 1,000 EST clusters
from rat. We discovered that Valproate regulated expression of 28 genes
including three isoenzymes (Yb, Yk and Yc) of glutathione S-transferase (GST),
which catalyzes the conjugation of oxidized products with the reduced
glutathione thiolate anion to form a non-toxic and excretable product, and which
plays an important protective role against oxidative stress.. Previous studies
in our laboratory found that chronic Valproate treatment protected cultured
neurons against oxidative damage to lipid and protein. Together these studies
suggested that regulation of GST may mediate the anti-oxidative effects of
Valproate. Currently we are using human 19k microarrays consisting of
robotically spotted, PCR amplified cDNAs on coated glass slides to analyze gene
expression profiles in post mortem frontal cortex from Stanley Medical Research
Institute in a larger group of BD subjects (35 for BD, 35 fro schizophrenia as
psychiatric disorder control, 35 for unaffected control).