A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18

Paola Bossù, Debora Cutuli, Ilaria Palladino, Paola Caporali, Francesco Angelucci, Daniela Laricchiuta, Francesca Gelfo, Paola De Bartolo, Carlo Caltagirone, Laura Petrosini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Systemic inflammation might cause neuronal damage and sustain neurodegenerative diseases and behavior impairment, with the participation of pro-inflammatory cytokines, like tumor necrosis factor (TNF)-α and interleukin (IL)-18. However, the potential contribution of these cytokines to behavioral impairment in the long-term period has not been fully investigated.Methods: Wistar rats were treated with a single intraperitoneal injection of LPS (5 mg/kg) or vehicle. After 7 days and 10 months, the animal behavior was evaluated by testing specific cognitive functions, as mnesic, discriminative, and attentional functions, as well as anxiety levels. Contextually, TNF-α and IL-18 protein levels were measured by ELISA in defined brain regions (that is, frontal cortex, hippocampus, striatum, cerebellum, and hypothalamus).Results: Behavioral testing demonstrated a specific and persistent cognitive impairment characterized by marked deficits in reacting to environment modifications, possibly linked to reduced motivational or attentional deficits. Concomitantly, LPS induced a TNF-α increase in the hippocampus and frontal cortex (from 7 days onward) and cerebellum (only at 10 months). Interestingly, LPS treatment enhanced IL-18 expression in these same areas only at 10 months after injection.Conclusions: Overall, these results indicate that the chronic neuroinflammatory network elicited by systemic inflammation involves a persistent participation of TNF-α accompanied by a differently regulated contribution of IL-18. This leads to speculation that, though with still unclear mechanisms, both cytokines might take part in long-lasting modifications of brain functions, including behavioral alteration.

Original languageEnglish
Article number101
JournalJournal of Neuroinflammation
Volume9
DOIs
Publication statusPublished - May 29 2012

Keywords

  • Behavioral impairment
  • Cerebellum
  • Cytokines
  • Frontal cortex
  • Hippocampus
  • Lipopolysaccharide (LPS)
  • Neuroinflammation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology
  • Neuroscience(all)

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