title: Corticosterone basal levels and vulnerability to LPS-induced neuroinflammation in the rat brain.
abstract: To assess whether the individual differences on the brain response to lipopolysaccharide (LPS) are correlated with the individual differences in the hypothalamus-pituitary-adrenal axis basal activity, adult male outbred rats were injected i.p. with 1 mg/kg LPS and evaluated after 4 h. Basal (1 week before LPS) and post-LPS plasma corticosterone (CC) were measured (mean basal: 225+/-22 ng/mL at 15:00 h). Group H was assigned to animals with 33% higher levels of CC (>234 ng/mL) and group L to animals with 33% lower levels of CC (<167 ng/mL). The H group showed an 8.8 times less relative increase of CC after LPS than the L group as well as a reduced glucocorticoid receptor upregulation after LPS. In addition, H individuals present higher plasma levels of TNF-alpha and IL-1beta after LPS. Interestingly, these animals are more vulnerable to the accumulation of oxidative/nitrosative mediators in the brain (NF-kappaB, NOS-2 and COX-2). Concomitantly, H animals are less protected against LPS-induced neuroinflammation, since anti-inflammatory mediators, lipocalin-prostaglandinD2 synthase and peroxisome proliferator-activated gamma, are downregulated after LPS. These data demonstrate that CC plasma basal levels might be a relevant parameter for predicting the individual response to LPS.
authors.affiliation: Dpt. of Pharmacology, Fac. Medicine, Univ. Complutense and CIBERSam. Madrid 28040, Spain.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Pérez-Nievas
authors.forename: José L M
authors.initials: JL
authors.lastname: Madrigal
authors.forename: Borja
authors.initials: B
authors.lastname: García-Bueno
authors.forename: Silvia
authors.initials: S
authors.lastname: Zoppi
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001831:Body Temperature / Q000502:physiology; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004660:Encephalitis / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D054834:Lipocalins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D054834:Lipocalins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D003345:Corticosterone