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Reduced [3H]cyclic AMP binding in postmortem brain from subjects with bipolar affective disorder
1Section of Biochemical Psychiatry, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Journal of Neurochemistry
|January 1, 1997
Summary
Bipolar disorder (BD) brain tissue shows reduced levels of cyclic AMP-dependent protein kinase (cAMP-dPK) regulatory subunits in the cytosol. This suggests altered cAMP signaling pathways may contribute to the neurobiology of bipolar disorder.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Bipolar disorder (BD) is associated with altered Gs alpha levels and adenylyl cyclase activity, suggesting dysregulated cyclic AMP (cAMP) signaling.
- Intracellular cAMP levels are known to influence the abundance and disposition of cAMP-dependent protein kinase (cAMP-dPK) regulatory subunits.
Purpose of the Study:
- To investigate whether hyperfunctional Gs alpha-linked cAMP signaling occurs in bipolar disorder.
- To determine the levels of cAMP-dPK regulatory subunits in postmortem brain tissue from individuals with BD.
Main Methods:
- Quantified [3H]cAMP binding, a measure of cAMP-dPK regulatory subunits, in cytosolic and membrane fractions of discrete brain regions from postmortem BD brains and matched controls.
- Compared [3H]cAMP binding in frontal, temporal, occipital, parietal cortex, cerebellum, and thalamus.
Main Results:
- Significantly reduced [3H]cAMP binding was observed in cytosolic fractions across all examined brain regions in BD patients compared to controls (-13% to -36%).
- No significant differences in [3H]cAMP binding were found in the membrane fractions.
Conclusions:
- The findings suggest alterations in cAMP-dPK regulatory subunits within the brain in bipolar disorder, potentially linked to increased cAMP signaling.
- The influence of antemortem treatments like lithium cannot be excluded as a contributing factor to these observed changes.