The anti-inflammatory prostaglandin 15d-PGJ2 and its nuclear receptor PPARgamma are decreased in schizophrenia

• Published in: Schizophrenia research Vol. 128; no. 1; pp. 15 - 22
• Main Authors: Martínez-Gras, Isabel, Pérez-Nievas, Beatriz G, García-Bueno, Borja, Madrigal, José L.M, Andrés-Esteban, Eva, Rodríguez-Jiménez, Roberto, Hoenicka, Janet, Palomo, Tomás, Rubio, Gabriel, Leza, Juan C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.05.2011
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Biological and medical sciences; Dinoprostone - blood; Female; Humans; Immunoenzyme Techniques - methods; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; NF-kappa B - blood; PPAR gamma - blood; Prostaglandin D2 - analogs & derivatives; Prostaglandin D2 - blood; Psychiatric Status Rating Scales; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - blood; Schizophrenia - pathology; Young Adult; Schizophrenia; Peripheral markers; Neuroinflammation, PGE 2, 15-d-PGJ 2, PPARγ; Human; Nuclear receptor; Prostaglandin; 15-d-PGJ; Arachidonic acid derivatives; Antiinflammatory agent; Neuroinflammation; PPARγ; PGE; Psychosis; Eicosanoid
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2011.01.018

Abstract A number of findings suggest that inflammation plays a role in the pathophysiology of schizophrenia. Taking into account a physiological balance between pro- and anti-inflammatory mediators, we measured the plasma levels of cyclooxygenase-derived mediators and other key pro- and anti-inflammatory transcription factors in peripheral blood mononuclear cells (PBMC). Forty healthy subjects and 46 treated chronic schizophrenic patients with an acutely exacerbated condition who met DSM-IV criteria were included. COX by-products prostaglandin E2 (PGE2 ) and 15d-prostaglandin J2 (15d-PGJ2 ) plasma levels were measured by EIA. Peroxisome proliferator-activated receptor gamma (PPARγ) as well as nuclear factor kappaB (NFκB) activity in nuclear extracts from PBMC and expression of its inhibitory subunit IκBα in cytosolic extracts were determined using ELISA-based kits. Schizophrenic patients showed higher plasma levels of pro-inflammatory PGE2 than age-matched controls ( p = 0.043). On the contrary, levels of anti-inflammatory 15-d-PGJ2 were lower ( p = 0.004), correlating with a lower expression of its nuclear target, PPARγ in nuclear extracts from PBMC ( p = 0.001). Although no changes in NFκB activity were observed between patients and healthy controls, the expression of its inhibitory protein IκBα was lower in the patients compared to the controls ( p = 0.027). These findings suggest that schizophrenia is associated with a systemic imbalance in the plasma levels of pro-inflammatory/anti-inflammatory prostaglandins in favor of the former. Furthermore, the expression and activity of anti-inflammatory PPARγ are diminished in PBMC, which indicates a state of inflammation and blunted anti-inflammatory counterbalancing mechanisms at systemic level in these patients.