title: Peroxisome proliferator-activated receptor gamma activation decreases neuroinflammation in brain after stress in rats.
abstract: BACKGROUND
  A growing body of evidence has demonstrated that peroxisome proliferator-activated receptor gamma (PPARgamma) play a role in brain inflammatory conditions because various PPARgamma ligands inhibit proinflammatory mediators, such as cytokines (tumor necrosis factor alpha [TNFalpha]) and inducible nitric oxide synthase (NOS-2). As has been previously shown, immobilization stress and stress-related neuropsychologic conditions are followed by accumulation of oxidative/nitrosative mediators in brain after the release of cytokines, nuclear factor kappaB activation, and NOS-2 and cyclooxygenase 2 (COX-2) expression in the brain.
  
  
  METHODS
  To assess whether PPARgamma activation can modify the accumulation of oxidative/nitrosative species seen in brain after stress, and to study the mechanisms by which this effect is achieved, young-adult male Wistar rats (control and immobilized during 6 hours) were injected (IP) with the high-affinity ligand rosiglitazone (RS) at the onset of stress.
  
  
  RESULTS
  Stress increased PPARgamma expression in cortical neurons and glia as assessed by Western blot and immunohistochemistry. In stressed animals, RS (1-3 mg/kg) decreased stress-induced increases in NOS-2 activity. On the other hand, the PPARgamma ligand decreased stress-induced malondialdehyde (an indicator of lipid peroxidation) accumulation in cortex and prevented oxidation of the main antioxidant glutathione. The mechanisms involved in the antioxidative properties of RS in stress involve nuclear factor KB blockade (by preventing stress-induced IkappaBalpha decrease) and inhibition of TNFalpha release in stressed animals. At the doses tested, RS did not decrease COX-2 expression and prostaglandin E2 release during stress. Finally, RS also decreased chronic (repeated immobilization for 21 days) stress-induced accumulation of oxidative/nitrosative mediators.
  
  
  CONCLUSIONS
  Taken together, these findings suggest a role for this antiinflammatory pathway in the brain response to stress and the possibility of pharmacologic modulation for preventing accumulation of oxidative/nitrosative species and subsequent brain damage in stress-related neuropsychologic conditions.
authors.affiliation: Department of Pharmacology, Faculty Medicine, University Complutense, Madrid, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.forename: José L M
authors.initials: JL
authors.lastname: Madrigal
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.forename: Pedro
authors.initials: P
authors.lastname: Lorenzo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D051546:Cyclooxygenase 2; D003600:Cytosol / Q000378:metabolism; D004660:Encephalitis / Q000473:pathology*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D047495:PPAR gamma; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D003345:Corticosterone