Postmortem cerebral cortex Gs alpha-subunit levels are elevated in bipolar affective disorder.
We examined the relative abundance of G-protein subunits in postmortem brain obtained from 7 patients with bipolar affective disorder (BAD) compared with 7 age- and sex-matched controls. G-protein subunit immunoreactivities were determined in membranes prepared from postmortem prefrontal cortex using SDS-PAGE and immunoblotting with specific polyclonal antisera against selected G-protein subunits: Gsa, Gi(1&2) alpha, Go alpha and G beta(1&2). Of these G-protein subunits, only Gs alpha immunoreactivity was found to be significantly elevated in frontal (+ 34%), and occipital (+ 80%) cortex (P less than 0.05) in BAD compared with control subjects. Smaller increments (+ 22%) in cerebellar Gs alpha immunoreactivity were also found but were not statistically significant. On the basis that increased Gs alpha immunoreactivity may reflect enhanced functional responsiveness of the receptor-effector units to which this coupling protein is integral, the present findings suggest that disturbances in Gs-mediated signal transduction may be involved in the pathophysiology of BAD.
Department of Psychiatry, University of Toronto, Clarke Institute of Psychiatry, Toronto, Canada.
L T
LT
Young
P P
PP
Li
S J
SJ
Kish
K P
KP
Siu
J J
JJ
Warsh
D001714:Bipolar Disorder / Q000378:metabolism*; D002525:Cerebellar Cortex / Q000737:chemistry*; D002540:Cerebral Cortex / Q000737:chemistry* / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis*; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009778:Occipital Lobe / Q000737:chemistry*; D011180:Postmortem Changes; D012016:Reference Values
D046911:Macromolecular Substances; D019204:GTP-Binding Proteins