Research Report Corticosterone basal levels and vulnerability to LPS-induced neuroinflammation in the rat brain Beatriz G. Pérez-Nievas, José L.M. Madrigal, Borja García-Bueno, Silvia Zoppi, Juan C. Leza ⁎ Dpt. of Pharmacology, Fac. Medicine, Univ. Complutense and CIBERSam. Madrid 28040, Spain ARTICLE INFO ABSTRACT Article history: Accepted 4 December 2009 Available online 21 December 2009 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-α and IL-1β after LPS. Interestingly, these animals are more vulnerable to the accumulation of oxidative/nitrosative mediators in the brain (NF-κB, 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. © 2009 Elsevier B.V. All rights reserved. Keywords: Corticosterone GR Vulnerability LPS Neuroinflammation 1. Introduction The bi-directional communication between the brain and the immune system forms a regulatory feedback system (Bese- dovsky et al., 1979), necessary to orchestrate the appropriate immunological, physiological, and behavioral responses to immune stimulation. According to this, immune stimuli activate stress pathways in the central nervous system (CNS) and in the periphery. Also, stressful stimuli alter functional aspects of the immune system (review in Kelley et al., 2003). Inflammatory signals induce CNS responsive cells to produce cytokines which target neuronal substrates and elicit a sickness behavior syndrome that is normally adaptive and beneficial to the host (review in Dantzer and Kelley, 2007). However, an excessive inflammatory cytokine response in brain is associated with a myriad of complications including cognitive dysfunction (learning and memory disruption) (Barrientos et al., 2006; Chen et al., 2008) and depressive-like behavior (Godbout et al., 2008). Lipopolysaccharide (LPS), also known as endotoxin, is a molecule on the outer portion of gram-negative bacteria which is one of the most potent inflammatory agents and is considered as a representative physiological stressor (Reyes et al., 2003). LPS has been used to study neuro-immune interac- tions due to its ability to reliably induce a rapid host response with cytokine release such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) (Meltzer et al., 2003). After intraperitoneal injection of LPS, a reaction of BRAIN RESEARCH 1315 (2010) 159 – 168 ⁎ Corresponding author. Departamento de Farmacología, Facultad de Medicina, UCM, Madrid 28040, Spain. Fax: +34 91 394 1464. E-mail address: jcleza@med.ucm.es (J.C. Leza). 0006-8993/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2009.12.014 available at www.sciencedirect.com www.elsevier.com/locate/brainres