J S Reiach1, P P Li, J J Warsh, S J Kish, L T Young. 1. Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
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, GTPgammaS- 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.
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, GTPgammaS- 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.
Authors: Matthew N Hill; Kim G C Hellemans; Pamela Verma; Boris B Gorzalka; Joanne Weinberg Journal: Neurosci Biobehav Rev Date: 2012-07-07 Impact factor: 8.989
Authors: Masahiro Fujita; Christina S Hines; Sami S Zoghbi; Alan G Mallinger; Leah P Dickstein; Jeih-San Liow; Yi Zhang; Victor W Pike; Wayne C Drevets; Robert B Innis; Carlos A Zarate Journal: Biol Psychiatry Date: 2012-06-05 Impact factor: 13.382
Authors: K Yaragudri Vinod; Suham A Kassir; Basalingappa L Hungund; Thomas B Cooper; J John Mann; Victoria Arango Journal: J Psychiatr Res Date: 2009-12-16 Impact factor: 4.791