Molecular Basis of Sickness Behavior DANTZER, ROBERT; BLUTHÉ, ROSE-MARIE; GHEUSI, GILLES ...
Annals of the New York Academy of Sciences,
1998-Sep-29, Letnik:
856, Številka:
1
Journal Article
Recenzirano
Peripheral and central injections of lipopolysaccharide (LPS), a cytokine inducer, and recombinant proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) induce sickness behavior in the ...form of reduced food intake and decreased social activities. Mechanisms of the behavioral effects of cytokines have been the subject of much investigation during the last 3 years. At the behavioral level, the profound depressing effects of cytokines on behavior are the expression of a highly organized motivational state. At the molecular level, sickness behavior is mediated by an inducible brain cytokine compartment that is activated by peripheral cytokines via neural afferent pathways. Centrally produced cytokines act on brain cytokine receptors that are similar to those characterized on peripheral immune and nonimmune cells, as demonstrated by pharmacologic experiments using cytokine receptor antagonists, neutralizing antibodies to specific subtypes of cytokine receptors, and gene targeting techniques. Evidence exists that different components of sickness behavior are mediated by different cytokines and that the relative importance of these cytokines is not the same in the peripheral and central cytokine compartments.
The present study was carried out to determine whether those factors which regulate the expression of IL-1β in immune and non-immune tissues are also able to regulate the expression of ICE. In a ...first experiment, mice were injected with LPS (10 μg/mouse, ip) and killed before, 1, 3 or 6 h after the injection. Total RNAs were extracted from the spleen, pituitary and brain (hippocampus and hypothalamus) and submitted to RT-PCR to determine the levels of ICE mRNA as compared to β2microglobulin mRNA. ICE mRNAs were more abundant in the spleen and hippocampus than in the pituitary and hypothalamus but they were not significantly altered by LPS treatment. In a second experiment mice were submitted to adrenalectomy or a 15 min restraint stress and injected with saline or LPS (10 μg/mouse, sc). They were killed 1–2 h later and total RNA was extracted from the same tissues as in experiment 1. Adrenalectomized mice had significantly higher ICE mRNA levels whereas stressed mice had significantly lower ICE mRNA levels than their respective controls. These results are discussed with respect to the possible regulatory influence of glucocorticoids on the expression of ICE.
The inflammatory state of the adipose tissue, in particular visceral adipose tissue, is believed to contribute to systemic chronic low-grade inflammation associated with obesity. Nevertheless, the ...precise characterization of the inflammatory profile of obese subjects, associating adipose and systemic inflammatory markers, is still needed. In addition, the question whether inflammatory specificities in obesity influence the outcomes of bariatric surgery, such as weight reduction, remains to be elucidated. To address these questions, thirty-seven obese patients were included in the present study and about 70% of them were followed up to fourteen months after bariatric surgery. Systemic concentrations of inflammatory markers were assessed using ELISA before bariatric surgery. Samples of visceral adipose tissue were extracted during bariatric surgery and gene expression of cytokines and immune cells markers were evaluated using qRT-PCR. Our results indicate that cytokines were strongly inter-correlated in the adipose tissue. In addition, we have found significant associations of adipose expression of macrophage and T cells markers with adipose expression and with systemic levels of cytokines, including TNF-α and IL-6. Importantly, a higher inflammatory state of the visceral adipose tissue before bariatric surgery predicted a lower weight reduction after surgery, notably at early stages post-surgery. Taking together, these findings highlight the importance of the inflammatory state of the visceral adipose tissue in obesity-related inflammation, and its relevance regarding its impact on outcomes of obesity treatments.
Microglial cells are an integral part of central nervous system networks. They were considered “resting,” but it has recently become evident that they actively sense neuronal microenvironment. In the ...developing brain, they contribute directly to the establishment of neuronal networks by eliminating or maintaining synapses. Morphofunctional plasticity of microglial cells is finely tuned in order to keep brain homeostasis and to ensure such developmental activity. N-6 and n-3 polyunsaturated fatty acids are essential fatty acids that have to be provided through the diet. They are precursors of bioactive lipid messengers involved in the regulation of inflammation and microglial activity. We previously demonstrated that depleting the diet in n-3 fatty acids from the first day of gestation alters some neuronal functions of the offspring at adulthood. We here hypothesized this is due to an alteration of microglial morphofunctional activity in the developing brain. Mice were submitted to a diet deficient or not in n-3 throughout gestation and lactation. Microglial morphology, phenotypes and functions were determined in the brain of pups at post-natal day 21. Microglial cells from mice fed with an n-3 deficient diet presented a drastic change of phenotype and a dysregulated activity. All together, our results show that dietary n-3 deficiency is likely to impair brain innate immune system activity at weaning. The outcome of such microglial impairment on brain function is discussed.
PDF
