prostaglandin-d2 and Depressive-Disorder--Major

Prostaglandin (PG) D2 is the most abundant prostaglandin in the mammalian brain. The physiological and pharmacological actions of PGD2 in the central nervous system seem to be associated with some of the symptoms exhibited by patients with major depressive disorder. Previous studies have found that PGD2 synthase was decreased in the cerebrospinal fluid of major depressive disorder patients. We speculated that there may be a dysregulation of PGD2 levels in major depressive disorder.. Ultra-performance liquid chromatography-tandem mass spectrometry coupled with a stable isotopic-labeled internal standard was used to determine PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice. A total of 32 drug-free major depressive disorder patients and 30 healthy controls were recruited. An animal model of depression was constructed by exposing mice to 5 weeks of chronic unpredictable mild stress. To explore the role of PGD2 in major depressive disorder, selenium tetrachloride was administered to simulate the change in PGD2 levels in mice.. Mice exposed to chronic unpredictable mild stress exhibited depression-like behaviors, as indicated by reduced sucrose preference and increased immobility time in the forced swimming test. PGD2 levels in the plasma of major depressive disorder patients and in the brains of depressive mice were both decreased compared with their corresponding controls. Further inhibiting PGD2 production in mice resulted in an increased immobility time in the forced swimming test that could be reversed by imipramine.. Decreased PGD2 levels in major depressive disorder are associated with depression-like behaviors.

Topics: Adolescent; Adult; Animals; Antidepressive Agents, Tricyclic; Antioxidants; Brain; Chromatography, Liquid; Depression; Depressive Disorder, Major; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Female; Food Preferences; Humans; Imipramine; Male; Mice; Mice, Inbred C57BL; Middle Aged; Prostaglandin D2; Selenium; Stress, Psychological; Swimming; Tandem Mass Spectrometry; Young Adult

The stimulatory guanine nucleotide binding protein Gs couples many cellular receptors to adenylate cyclase, and the Gsα subunit activates all 9 isoforms of the adenylate cyclase catalytic unit to produce the enzyme product cyclicAMP or cAMP. In prefrontal cortex and cerebellum of unipolar depressive suicides, Rasenick and colleagues have found increased concentrations of Gsα in membrane lipid microdomains (Donati et al., 2008), where the ensconced Gsα is less likely to activate adenylate cyclase by receptor and postreceptor pathways (Allen et al., 2005, 2009). We report that a group of 7 depressed patients (DP-1) had (1) reduced activation of platelet receptor-stimulated adenylate cyclase by both prostaglandins E2 and D2 compared to controls, and (2) reduced postreceptor stimulation of adenylate cyclase by aluminum fluoride ion in both platelets and mononuclear leukocytes when compared to both another group of depressed patients (DP-2, n = 17) and to controls (n = 21). Our observations in the blood cells of the group DP-1 support the findings of Donati et al. (2008), and they reflect the importance of this interaction between the activated Gsα subunit and membrane lipid microdomains in the pathophysiology and treatment of some major depressive disorders.

Topics: Adenylyl Cyclases; Adult; Aluminum Compounds; Blood Cells; Blood Platelets; Depressive Disorder, Major; Dinoprostone; Female; Fluorides; GTP-Binding Protein alpha Subunits, Gs; Humans; Lymphocytes; Male; Membrane Microdomains; Middle Aged; Prostaglandin D2; Prostaglandins