Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar affective disorder

Shafiqur Rahman, Peter P. Li, L. Trevor Young, Ora Kofman, Stephen J. Kish, Jerry J. Warsh

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Findings of increased G(s)α levels and forskolin-stimulated adenylyl cyclase activity in selective cerebral cortical postmortem brain regions in bipolar affective disorder (BD) implicate increased cyclic AMP (cAMP)- mediated signaling in this illness. Accumulating evidence suggests that intracellular levels of cAMP modulate the abundance and disposition of the regulatory subunits of cAMP-dependent protein kinase (cAMP-dPK). Thus, in the present study, we tested further whether hyperfunctional G(s)α-linked cAMP signaling occurs in BD by determining [3H]cAMP binding, a measure of the levels of regulatory subunits of cAMP-dPK, in cytosolic and membrane fractions from discrete brain regions of postmortem BD brain. Specific [3H]cAMP (5 nM) binding was determined in autopsied brain obtained from 10 patients with DSM-III-R diagnoses of BD compared with age- and postmortem delay-matched controls. [3H]cAMP binding was significantly reduced across all brain regions in cytosolic fractions of BD frontal (22%), temporal (- 23%), occipital (-22%) and parietal (-15%) cortex, cerebellum (-36%), and thalamus (-13%) compared with controls, but there were no differences in [3H]cAMP binding in the membrane fractions from these same regions. These results suggest that changes occur in the cAMP-dPK regulatory subunits in BD brain, possibly resulting from increased cAMP signaling. The possibility that antemortem lithium and/or other mood stabilizer treatment may contribute to the above changes, however, cannot be ruled out.

Original languageEnglish
Pages (from-to)297-304
Number of pages8
JournalJournal of Neurochemistry
Volume68
Issue number1
DOIs
StatePublished - 1 Jan 1997

Keywords

  • Bipolar affective disorder
  • Cyclic AMP-dependent protein kinase
  • Lithium
  • Postmortem brain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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