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

被引:63
作者
Martinez-Gras, Isabel [1 ,3 ,4 ]
Perez-Nievas, Beatriz G. [2 ,3 ,4 ]
Garcia-Bueno, Borja [2 ,3 ,4 ]
Madrigal, Jose L. M. [2 ,3 ,4 ]
Andres-Esteban, Eva [5 ,6 ]
Rodriguez-Jimenez, Roberto [1 ,3 ,4 ]
Hoenicka, Janet [1 ,3 ,4 ]
Palomo, Tomas [1 ,3 ,4 ]
Rubio, Gabriel [1 ,3 ,4 ]
Leza, Juan C. [2 ,3 ,4 ]
机构
[1] Univ Complutense, Fac Med, Dept Psychiat, E-28040 Madrid, Spain
[2] Univ Complutense, Fac Med, Dept Pharmacol, E-28040 Madrid, Spain
[3] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain
[4] Hosp 12 Octubre 1 12, Inst Invest Sanitaria, Madrid, Spain
[5] CIBER Epidemiol & Publ Hlth, Madrid, Spain
[6] Clin Epidemiol Unit, Madrid, Spain
关键词
Schizophrenia; Peripheral markers; Neuroinflammation; PGE(2); 15-d-PGJ(2); PPAR gamma; C-REACTIVE PROTEIN; SERUM-LEVELS; PPAR-GAMMA; DEPRESSION; INFLAMMATION; STRESS; ACTIVATION; CYTOKINES; DRUGS; ALPHA;
D O I
10.1016/j.schres.2011.01.018
中图分类号
R749 [精神病学];
学科分类号
100204 [神经病学];
摘要
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 E-2 (PGE(2)) and 15d-prostaglandin J(2) (15d-PGJ(2)) plasma levels were measured by EIA. Peroxisome proliferator-activated receptor gamma (PPAR gamma) as well as nuclear factor kappaB (NF kappa B) activity in nuclear extracts from PBMC and expression of its inhibitory subunit I kappa B alpha in cytosolic extracts were determined using ELISA-based kits. Schizophrenic patients showed higher plasma levels of pro-inflammatory PGE(2) than age-matched controls (p = 0.043). On the contrary, levels of anti-inflammatory 15-d-PGJ(2) were lower (p = 0.004), correlating with a lower expression of its nuclear target. PPAR gamma in nuclear extracts from PBMC (p = 0.001). Although no changes in NF kappa B activity were observed between patients and healthy controls, the expression of its inhibitory protein I kappa B alpha 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 PPAR gamma are diminished in PBMC, which indicates a state of inflammation and blunted anti-inflammatory counterbalancing mechanisms at systemic level in these patients. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:15 / 22
页数:8
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