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Fever is triggered by an elevation of prostaglandin E(2) (PGE(2)) in the brain. However, the mechanism of its elevation remains unanswered. We herein cloned the rat glutathione-dependent microsomal prostaglandin E synthase (mPGES), the terminal enzyme for PGE(2) biosynthesis, and examined its induction in the rat brain after intraperitoneal injection of(More)
The appetite suppressing hormone, leptin is now established as an important component of the immune response to pathogens partly via the induction of brain IL-1beta. We have previously demonstrated that this hormone acts on microglia to induce the release of IL-1beta through actions on its functional receptors. In the present study, we extended these(More)
The appetite suppressing hormone leptin has emerged as an important modulator of immune function and is now considered to be a critical link between energy balance and host defense responses to pathogens. These 'adaptive' responses can, in situations of severe and sustained systemic inflammation, lead to adverse effects including brain damage that is partly(More)
The noisy fluctuation of chemical reactions should profoundly affect the oscillatory dynamics of gene circuit. In this paper a prototypical genetic oscillator, repressilator, is numerically simulated to analyze effects of noise on oscillatory dynamics. The oscillation is coherent when the protein number and the rate of the DNA state alteration are within(More)
Exposure to a stressor sensitizes behavioral and hormonal responses to future stressors. Stress-associated release of noradrenaline enhances the capacity of central synapses to show plasticity (metaplasticity). We found noradrenaline-dependent metaplasticity at GABA synapses in the paraventricular nucleus of the hypothalamus in rat and mouse that controls(More)
Stressful experience initiates a neuroendocrine response culminating in the release of glucocorticoid hormones into the blood. Glucocorticoids feed back to the brain, causing adaptations that prevent excessive hormone responses to subsequent challenges. How these changes occur remains unknown. We found that glucocorticoid receptor activation in rodent(More)
In addition to its central effects on appetite regulation, leptin has been implicated in immune function and inflammation. Previous data suggested that leptin acts as an inflammatory signal within the brain, as exogenously administered leptin induced fever, a typical brain-regulated inflammatory response. The present study aimed to delineate the(More)
Leptin regulates energy balance by suppressing appetite and increasing energy expenditure through actions in the hypothalamus. Recently we demonstrated that the effects of leptin are, at least in part, mediated by the release of interleukin (IL)-1beta in the brain. Microglia constitute the major source of IL-1beta in the brain but it is not known whether(More)
This study aimed to address the relative contributions of the proinflammatory cytokine interleukin-6 (IL-6) and the cytokine-like hormone leptin to the genomic activation of brain cells during lipopolysaccharide (LPS)-induced systemic inflammation. Wildtype and IL-6KO mice were injected with LPS (50 microg/kg, intraperitoneally) and the brains analyzed by(More)
Global levels of obesity are reaching epidemic proportions, leading to a dramatic increase in incidence of secondary diseases and the significant economic burden associated with their treatment. These comorbidities include diabetes, cardiovascular disease, and some psychopathologies, which have been linked to a low-grade inflammatory state. Obese(More)