A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18.
J Neuroinflammation
; 9: 101, 2012 May 29.
Article
em En
| MEDLINE
| ID: mdl-22642744
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Fator de Necrose Tumoral alfa
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Aprendizagem em Labirinto
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Interleucina-18
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Endotoxinas
Limite:
Animals
Idioma:
En
Revista:
J Neuroinflammation
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Itália