High levels of Gs alpha in platelets of euthymic patients with bipolar affective disorder

doi:10.1176/ajp.154.2.218

Cited by 46 publications

(3 citation statements)

References 35 publications

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“…The G protein-bound adenylate cyclase catalyzes the conversion of ATP into c-AMP, which activates PKA, which in turn regulates several intracellular processes including phosphorylation of CREB, a transcription factor [136]. Increased c-AMP signaling is also implicated in BD [137,138,139]. In vivo microdialysis revealed that direct activation of PKC by PMA in the frontal cortex and hippocampus increases c-AMP in the dialysate [39].…”

Section: Downstream Targets Of Pkcmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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Bipolar disorder (BD) is a major health problem. It causes significant morbidity and imposes a burden on the society. Available treatments help a substantial proportion of patients but are not beneficial for an estimated 40-50%. Thus, there is a great need to further our understanding the pathophysiology of BD to identify new therapeutic avenues. The preponderance of evidence pointed towards a role of protein kinase C (PKC) in BD. We reviewed the literature pertinent to the role of PKC in BD. We present recent advances from preclinical and clinical studies that further support the role of PKC. Moreover, we discuss the role of PKC on synaptogenesis and neuroplasticity in the context of BD. The recent development of animal models of BD, such as stimulant-treated and paradoxical sleep deprivation, and the ability to intervene pharmacologically provide further insights into the involvement of PKC in BD. In addition, the effect of PKC inhibitors, such as tamoxifen, in the resolution of manic symptoms in patients with BD further points in that direction. Furthermore, a wide variety of growth factors influence neurotransmission through several molecular pathways that involve downstream effects of PKC. Our current understanding identifies the PKC pathway as a potential therapeutic avenue for BD.

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Section: Downstream Targets Of Pkcmentioning

confidence: 99%

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

et al. 2017

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“…Several studies have shown that mRNA levels for Gαs, the stimulatory G-protein that couples with AC, are increased in peripheral cells of BPD patients. 30, 31, 32, 33, 34 Post-mortem analyses on brain have demonstrated an increased abundance of the Gαs protein, but not Gαi or Gαo, 32, 30 and lithium has been found to decrease the abundance of mRNAs for several G-proteins. 35, 36 Lithium may also decrease the coupling of receptors to G-proteins.…”

Section: Introductionmentioning

confidence: 99%

Genetic association of cyclic AMP signaling genes with bipolar disorder

McDonald

MacMullen

et al. 2012

Transl Psychiatry

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The genetic basis for bipolar disorder (BPD) is complex with the involvement of multiple genes. As it is well established that cyclic adenosine monophosphate (cAMP) signaling regulates behavior, we tested variants in 29 genes that encode components of this signaling pathway for associations with BPD type I (BPD I) and BPD type II (BPD II). A total of 1172 individuals with BPD I, 516 individuals with BPD II and 1728 controls were analyzed. Single SNP (single-nucleotide polymorphism), haplotype and SNP × SNP interactions were examined for association with BPD. Several statistically significant single-SNP associations were observed between BPD I and variants in the PDE10A gene and between BPD II and variants in the DISC1 and GNAS genes. Haplotype analysis supported the conclusion that variation in these genes is associated with BPD. We followed-up PDE10A's association with BPD I by sequencing a 23-kb region in 30 subjects homozygous for seven minor allele risk SNPs and discovered eight additional rare variants (minor allele frequency <1%). These single-nucleotide variants were genotyped in 999 BPD cases and 801 controls. We obtained a significant association for these variants in the combined sample using multiple methods for rare variant analysis. After using newly developed methods to account for potential bias from sequencing BPD cases only, the results remained significant. In addition, SNP × SNP interaction studies suggested that variants in several cAMP signaling pathway genes interact to increase the risk of BPD. This report is among the first to use multiple rare variant analysis methods following common tagSNPs associations with BPD.

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“…Abnormalities in G proteins coupled to cAMP signaling have also been reported in patients with bipolar disorder [ 34 , 39 , 40 , 41 , 42 , 43 , 44 ] and may potentially lead to dysfunctions of the downstream components of the cAMP dependent phosphorylation such as PKA and Rap1.…”

Section: G Proteins and Adenylyl Cyclase-camp And Their Role In Dementioning

confidence: 99%

Glycosides, Depression and Suicidal Behaviour: The Role of Glycoside-Linked Proteins

et al. 2011

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Nowadays depression and suicide are two of the most important worldwide public health problems. Although their specific molecular mechanisms are still largely unknown, glycosides can play a fundamental role in their pathogenesis. These molecules act presumably through the up-regulation of plasticity-related proteins: probably they can have a presynaptic facilitatory effect, through the activation of several intracellular signaling pathways that include molecules like protein kinase A, Rap-1, cAMP, cADPR and G proteins. These proteins take part in a myriad of brain functions such as cell survival and synaptic plasticity. In depressed suicide victims, it has been found that their activity is strongly decreased, primarily in hippocampus and prefrontal cortex. These studies suggest that glycosides can regulate neuroprotection through Rap-1 and other molecules, and may play a crucial role in the pathophysiology of depression and suicide.

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High levels of Gs alpha in platelets of euthymic patients with bipolar affective disorder

Cited by 46 publications

References 35 publications

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

Genetic association of cyclic AMP signaling genes with bipolar disorder

Glycosides, Depression and Suicidal Behaviour: The Role of Glycoside-Linked Proteins

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