A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18.
A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18.
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DOI：
10.1186/1742-2094-9-101
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发表时间：
2012-05-29
影响因子：
9.3
通讯作者：
Petrosini L
中科院分区：
文献类型：
--
作者：
Bossù P;Cutuli D;Palladino I;Caporali P;Angelucci F;Laricchiuta D;Gelfo F;De Bartolo P;Caltagirone C;Petrosini L
全身性炎症可引起神经元损伤，并维持神经退行性疾病和行为障碍，促炎细胞因子如肿瘤坏死因子（TNF）-α和白细胞介素（IL）-18参与其中。然而，这些细胞因子对长期行为障碍的潜在贡献尚未得到充分研究。Wistar大鼠用单次腹膜内注射LPS（5 mg/kg）或媒介物处理。7天和10个月后，通过测试特定的认知功能（如记忆、辨别和注意力功能）以及焦虑水平来评估动物行为。在背景下，通过ELISA测定了特定脑区（即额叶皮质、海马、纹状体、小脑和下丘脑）的TNF-α和IL-18蛋白水平。行为测试表明，一个特定的和持久的认知功能障碍，其特征是显着的赤字，在对环境的修改，可能与减少动机或注意力缺陷。同时，LPS诱导海马和额叶皮质（从7天开始）和小脑（仅在10个月时）中的TNF-α增加。有趣的是，LPS治疗仅在注射后10个月增强了这些相同区域中的IL-18表达。总体而言，这些结果表明，全身性炎症引起的慢性神经炎症网络涉及TNF-α的持续参与，伴随着IL-18的不同调节作用。这引发了一种猜测，尽管机制尚不清楚，但这两种细胞因子可能参与了大脑功能的长期改变，包括行为改变。
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. 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). 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. 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.
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影响因子：
3.3
作者：
Curran, B;O'Connor, JJ
通讯作者：
O'Connor, JJ
影响因子：
9.3
作者：
Alboni S;Cervia D;Sugama S;Conti B
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影响因子：
15.1
作者：
Barrientos, Ruth M.;Watkins, Linda R.;Rudy, Jerry W.;Maier, Steven F.
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影响因子：
16.8
作者：
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通讯作者：
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影响因子：
4.7
作者：
GLOWINSKI, J;IVERSEN, LL
通讯作者：
IVERSEN, LL