Reduced adenylyl cyclase immunolabeling and activity in postmortem temporal cortex of depressed suicide victims

Abstract

Background: Previous studies have found altered receptor/G protein-modulated adenylyl cyclase (AC) activity in subjects with mood disorders. Methods: To investigate whether these effects are associated with altered levels of specific isoforms of AC, we measured AC isoform I, IV and V/VI immunoreactivities in postmortem temporal cortex from nine depressed suicide victims, nine subjects with bipolar disorder (BD) and 18 age-matched non-psychiatric controls. Basal, GTPγS- and forskolin-stimulated AC activities were measured in the temporal cortex from the nine depressed suicide victims and their controls. Results: Western blotting revealed significant reductions in immunolabeling in AC type IV (−49%; p<0.05) in depressed suicide subjects compared to age-matched controls, but no differences were found in AC type I or type V/VI. There were no statistically significant differences in AC type I, IV or V/VI immunoreactivities between BD and matched control subjects. Functionally, there was a significant reduction in forskolin-stimulated AC activity in depressed suicide subjects compared to controls, which may be, in part, related to higher basal AC activity in the former group. Limitations: Our sample size was small with diverse subject characteristics. Conclusions: These preliminary findings suggest altered levels and/or function in AC type IV may contribute to disturbances in the postreceptor cAMP signaling cascade in depression.