Anatomic patterns of FOS immunostaining in rat brain following systemic endotoxin administration

Sagar, Stephen M.; Price, Kristen; Kasting, Norman W.; Sharp, Frank R.

doi:10.1016/0361-9230(94)00217-o

Cited by 135 publications

(97 citation statements)

References 43 publications

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“…In the present report, we show that inactivation of NFkB at the blood-brain interface inhibits both the cerebral activation response to peripheral IL-1b, as measured by expression of the early activated protein c-Fos (Sagar et al, 1995) and the behavioral alterations induced by intraperitoneally administered IL-1b.…”

Section: Introductionsupporting

confidence: 54%

Inactivation of the Cerebral NFκB Pathway Inhibits Interleukin-1β-Induced Sickness Behavior and c-Fos Expression in Various Brain Nuclei

Nadjar

Bluthé

May

et al. 2005

Neuropsychopharmacol

111

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The behavioral effects of peripherally administered interleukin-1b (IL-1b) are mediated by the production of cytokines and other proinflammatory mediators at the level of the blood-brain interface and by activation of neural pathway. To assess whether this action is mediated by NFkB activation, rats were injected into the lateral ventricle of the brain with a specific inhibitor of NFkB activation, the NEMO Binding Domain (NBD) peptide that has been shown previously to abolish completely IL-1b-induced NFkB activation and Cox-2 synthesis in the brain microvasculature. NFkB pathway inactivation significantly blocked the behavioral effects of intraperitoneally administered IL-1b in the form of social withdrawal and decreased food intake, and dramatically reduced IL-1b-induced c-Fos expression in various brain regions as paraventricular nucleus, supraoptic nucleus, and lateral part of the central amygdala. These findings strongly support the hypothesis that IL-1b-induced NFkB activation at the blood-brain interface is a crucial step in the transmission of immune signals from the periphery to the brain that underlies further events responsible of sickness behavior.

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Section: Introductionsupporting

confidence: 54%

Inactivation of the Cerebral NFκB Pathway Inhibits Interleukin-1β-Induced Sickness Behavior and c-Fos Expression in Various Brain Nuclei

Nadjar

Bluthé

May

et al. 2005

Neuropsychopharmacol

111

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“…35 These brain stem regions provide massive projections to the paraventricular nucleus, the pathways believed to play a role in the mediation of the effects of immune challenges and systemic cytokines on hypothalamic neuroendocrine response. 36 Wan et al 7 demonstrated that prostaglandin synthesis and visceral-vagal afferents are involved in the LPS-activated c-fos protein expression in specific autonomic and neuroendocrine nuclei in the brain. It is tempting to speculate that NO and glutamate may be at least partially responsible for the induction of c-fos protein in the brain stem nuclei.…”

Section: Discussionmentioning

confidence: 99%

Systemic Administration of Lipopolysaccharide Induces Release of Nitric Oxide and Glutamate and c- fos Expression in the Nucleus Tractus Solitarii of Rats

Wan

Kang

et al. 1999

Hypertension

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Abstract-There is increasing recognition that communication pathways exist between the immune system and brain, which allows bidirectional regulation of immune and brain responses to infection. The endotoxin lipopolysaccharide (LPS) has been reported to elicit release of cytokines and expression of inducible nitric oxide synthase (iNOS) in peripheral organs. Whereas LPS given systemically causes endotoxic shock, little is known about its central nervous system action, particularly the induction of iNOS. Nitric oxide (NO) and glutamate in the nucleus tractus solitarii (NTS) are important mediators of central cardiovascular regulation. We have previously demonstrated that intravenous injections of LPS increased the NO precursor L-arginine-induced depressor effect in the NTS. The present study investigated further the effects of LPS on the release of NO and glutamate in the NTS and the expression of c-fos, an immediate early response gene product, in neural substrates for central cardiovascular control. In vivo microdialysis coupled with chemiluminescence and electrochemical detection techniques were used to measure extracellular levels of NO and glutamate in the rat NTS. Immunohistochemistry was used for the examination of c-fos protein expression. We found that intravenous infusion of LPS (10 mg/kg) produced a biphasic depressor effect, with an early, sharp hypotension that partially recovered in 15 minutes and a secondary, more prolonged hypotension. In the NTS, a progressive increase of extracellular glutamate and NO levels occurred 3 and 4 hours after LPS was given, respectively. The effects of LPS on the induction of delayed hypotension and NO formation in the NTS were abolished by pretreatment with the iNOS inhibitor aminoguanidine. Finally, c-fos protein expression in the NTS and related structures for cardiovascular regulation was observed after LPS challenge. Taken together, these data suggest that an endotoxin given systemically can elicit delayed increases of glutamate release and iNOS-dependent NO production in the NTS and activate the central neural pathway for modulating cardiovascular function. (Hypertension. 1999;33:1218-1224.)Key Words: nitric oxide synthase Ⅲ endotoxin Ⅲ cardiovascular system Ⅲ microdialysis N itric oxide (NO), a free-radical gas produced from L-arginine by the enzyme NO synthase (NOS), is a remarkable regulatory molecule that plays an important role in a variety of physiological functions. Several isoforms of NOS have been isolated and purified. The NOS in endothelial (eNOS) and neuronal (nNOS) cells are expressed constitutively, and their activities are regulated by changes in intracellular calcium. In contrast, activation of macrophages with endotoxins and/or cytokines results in the de novo biosynthesis of a calcium-independent (inducible) isoform of NOS (iNOS). 1 The iNOS-mediated NO formation induced by endotoxins is responsible for the fall of blood pressure in endotoxic shock. 2 The endotoxin lipopolysaccharide (LPS) is a unique glucosamine-based phospholipid that makes u...

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“…In addition to anxiolytic agents, c-Fos expression is induced in the CeL by different types of pharmacological agents, including anxiogenic compounds (Bittencourt and Sawchenko, 2000;Singewald and Sharp, 2000;Day et al, 2001), severe stress (Chowdhury et al, 2000), and peripheral autonomic challenges (McKitrick et al, 1992;Sagar et al, 1995). Clearly, c-Fos induction in the CeL is not specific for anxiolytic agents.…”

Section: Central C-fos After Anxiolytic Ly354740mentioning

confidence: 99%

Anxiolytic Activity of the MGLU2/3 Receptor Agonist LY354740 on the Elevated Plus Maze is Associated with the Suppression of Stress-Induced c-Fos in the Hippocampus and Increases in c-Fos Induction in Several Other Stress-Sensitive Brain Regions

Lindén

Greene

Bergeron

et al. 2003

Neuropsychopharmacol

101

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LY354740 is a potent and selective agonist for group II metabotropic glutamate (mGlu) receptors, mGlu2 and mGlu3 receptors, with anxiolytic activity in several animal models of anxiety, including the elevated plus maze (EPM) test. Here, we studied neuronal activation in mouse brain after EPM exposure in saline-and LY354740-treated mice using c-Fos immunoreactivity as a marker. The effect of LY354740 on c-Fos expression was also studied in cage control (no EPM) mice. Pretreatment with LY354740 (20 mg/kg, s.c.) produced robust anxiolytic behavior on the EPM. LY354740 administration decreased EPM-induced increases in c-Fos expression in the CA3 of the hippocampus, while having no significant effects on basal c-Fos expression in the hippocampus. LY354740 administration significantly increased c-Fos expression in specific limbic regions, including the lateral division of the central nucleus of the amygdala (CeL), lateral parabrachial nucleus, locus coeruleus, and Edinger-Westphal nucleus, whether or not animals were exposed to the EPM. Moreover, LY354740 administration per se significantly increased c-Fos expression in regions processing sensory information, including the paraventricular and lateral geniculate nucleus of the thalamus as well as the nucleus of the optic tract and superior colliculus. In particular, the suppression of fear-evoked neuronal activity in the hippocampus and drug-induced increases in neuronal activation in the CeL have been previously linked to the anxiolytic effects of clinically effective drugs such as benzodiazepines, and thus may contribute to anxiolytic actions of LY354740 in animal models and human anxiety patients.

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Anatomic patterns of FOS immunostaining in rat brain following systemic endotoxin administration

Cited by 135 publications

References 43 publications

Inactivation of the Cerebral NFκB Pathway Inhibits Interleukin-1β-Induced Sickness Behavior and c-Fos Expression in Various Brain Nuclei

Inactivation of the Cerebral NFκB Pathway Inhibits Interleukin-1β-Induced Sickness Behavior and c-Fos Expression in Various Brain Nuclei

Systemic Administration of Lipopolysaccharide Induces Release of Nitric Oxide and Glutamate and c- fos Expression in the Nucleus Tractus Solitarii of Rats

Anxiolytic Activity of the MGLU2/3 Receptor Agonist LY354740 on the Elevated Plus Maze is Associated with the Suppression of Stress-Induced c-Fos in the Hippocampus and Increases in c-Fos Induction in Several Other Stress-Sensitive Brain Regions

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