Citation

Odagaki Y, García-Sevilla JA, Huguelet P, La Harpe R, Koyama T, Guimón J. Brain Res. 2001; 898(2): 224-231.

Copyright

(Copyright © 2001, International Brain Research Organization, Publisher Elsevier Publishing)

DOI

10.1016/s0006-8993(01)02188-6

PMID

11306008

Abstract

The components of cyclic AMP signaling cascade (catalytic (Calpha) subunit of cyclic AMP-dependent protein kinase (PKA) and cyclic AMP response element binding protein (CREB)) were quantitated by Western blotting in the prefrontal cortex of depressed suicide victims (n=23) and their matched controls (n=14). There was a significant increase in the levels of CREB, both in total (tCREB; 121+/-8% (mean+/-S.E.M.), P<0.02) and phosphorylated (pCREB; 128+/-9%, P<0.01) forms, but not in PKA Calpha levels (109+/-9%, ns), in brains of depressed suicides compared to those in control subjects. The increases in CREB were specifically observed in antidepressant drug-free subjects (tCREB: 137+/-11%, P<0.01; pCREB: 136+/-12%, P<0.02; n=9), but not in the antidepressant-treated subjects (tCREB: 108+/-18%, ns; pCREB: 111+/-17%, ns; n=8). There were significant correlations between the levels of PKA and those of tCREB and pCREB in the prefrontal cortex of depressed suicides. These results indicate that the components of cyclic AMP signaling are upregulated in a coordinated manner in brains of depressed suicides and that this alteration is not related to antidepressant treatment.

Language: en

Keywords

Adult; Antidepressive Agents; Biomarkers; Brain Chemistry; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Depression; Female; Humans; Immunohistochemistry; Male; Middle Aged; Phosphorylation; Prefrontal Cortex; Signal Transduction; Suicide; Up-Regulation