RT Journal Article
SR Electronic
T1 Postmortem Brain Tissue of Depressed Suicides Reveals Increased Gsα Localization in Lipid Raft Domains Where It Is Less Likely to Activate Adenylyl Cyclase
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3042
OP 3050
DO 10.1523/JNEUROSCI.5713-07.2008
VO 28
IS 12
A1 Donati, Robert J.
A1 Dwivedi, Yogesh
A1 Roberts, Rosalinda C.
A1 Conley, Robert R.
A1 Pandey, Ghanshyam N.
A1 Rasenick, Mark M.
YR 2008
UL http://www.jneurosci.org/content/28/12/3042.abstract
AB Recent in vivo and in vitro studies have demonstrated that Gsα migrates from a Triton X-100 (TX-100)-insoluble membrane domain (lipid raft) to a TX-100-soluble nonraft membrane domain in response to chronic, but not acute, treatment with tricyclic or selective serotonin reuptake inhibitor antidepressants. This migration resulted in a more facile association with adenylyl cyclase. Our hypothesis is that Gsα may be ensconced, to a greater extent, in lipid rafts during depression, and that one action of chronic antidepressant treatment is to reverse this. In this postmortem study, we examined Gsα membrane localization in the cerebellum and prefrontal cortex of brains from nonpsychiatric control subjects and suicide cases with confirmed unipolar depression. Sequential TX-100 and TX-114 detergent extractions were performed on the brain tissue. In the cerebellum, the ratio of TX-100/TX-114-soluble Gsα is ∼2:1 for control versus depressed suicides. Results with prefrontal cortex samples from each group demonstrate a similar trend. These data suggest that depression localizes Gsα to a membrane domain (lipid rafts) where it is less likely to couple to adenylyl cyclase and that antidepressants may upregulate Gsα signaling via disruption of membrane microenvironments. Raft localization of Gsα in human peripheral tissue may thus serve as a biomarker for depression and as a harbinger of antidepressant responsiveness.