Reduced mRNA expression of PTGDS in peripheral blood mononuclear cells of rapid-cycling bipolar disorder patients compared with healthy control subjects.
Bottom Line: We aimed to test the hypothesis that mRNA expression of PTGDS and AKR1C3 is deregulated in rapid-cycling disorder patients in a euthymic or current affective state compared with healthy control subjects, and that expression alters with affective states.Repeated measurements of PTGDS and AKR1C3 mRNA expression were obtained in various affective states during 6-12 months and compared with repeated measurements in healthy control subjects.No difference in PTGDS mRNA expression was observed between affective states.
Affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark (Drs Munkholm, Kessing, and Vinberg); Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark (Dr Peijs). firstname.lastname@example.org.Show MeSH
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Mentions: Arachidonic acid, particularly abundant in the brain, is a polyunsaturated fatty acid present in the cell membrane phospholipids, from which it is freed by cytosolic phospholipase A2 (cPLA2; Rapoport, 2014). The isoenzyme cPLA2 IVA is selective for AA hydrolysis and its activity is modulated by lithium and carbamazepine (Rapoport et al., 2009; Berg et al., 2010). The expression of cPLA2 IVA, as well as of the cyclooxygenase (COX)-2 enzyme, has been found to be altered in the post-mortem brain tissue of bipolar disorder patients (Kim et al., 2011). AA acts as a precursor in the production of prostaglandin H2 (PGH2), mediated by COX, which, in turn, is converted to prostaglandins, thromboxanes, or prostacyclins (Funk, 2001). The conversion of PGH2 to prostaglandin D2 (PGD2) is catalyzed by prostaglandin D synthase (PTGDS), encoded by the PTGDS gene, and preferentially expressed in the brain. PGD2 functions as a neuromodulator as well as a trophic factor in the central nervous system (Taniguchi et al., 2007) and is preferentially expressed in the brain. Reduction of both PGH2 and PGD2 is catalyzed by the aldo-keto reductase family 1 member C3 (AKR1C3) enzyme, encoded by the AKR1C3 gene, resulting in synthesis of prostaglandin F2 alpha (Figure 1).
Affiliation: Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark (Drs Munkholm, Kessing, and Vinberg); Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark (Dr Peijs). email@example.com.