The cAMP-dependent protein kinase A and brain-derived neurotrophic factor expression in lymphoblast cells of bipolar affective disorder

Background: Abnormalities in cAMP signaling and altered expression of downstream targets such as brain-derived neurotrophic factor (BDNF) have been postulated in patients with bipolar disorder (BD). Methods: The PKA activity and levels of 3H–cAMP binding to PKA R regulatory subunits were measured in lymphoblasts from 10 BD and 10 control subjects. In addition, the possibility that BDNF expression could be altered in these cells has been explored. Results: Results indicate that PKA activity significantly increased (t-test; P<0.01), whereas the 3H–cAMP binding to PKA R subunits decreased in cells from BD (t-test; P<0.02). The presence of 10 μM Sp–cAMP in culture 24 h before cell harvesting induced an increase in enzyme activity and a decrease in 3H–cAMP binding sites (t-test; P<0.01), with a significant difference between BD and controls (t-test; P<0.01). This presence of Sp–cAMP also results in increased BDNF expression (t-test, P<0.01), but neither in resting cells, nor in stimulated cells, was any difference observed in BDNF expression between BD and controls (t-test, NS). Limitations: This study was conducted on a peripheral model cell, whose importance of BDNF is unknown. Conclusion: These data suggest that the upregulation of cAMP signaling observed in BD patients results in the normalization of the BDNF expression. Studies on signal transduction, gene expression and pathologies have implications for development of novel treatments.