Presynaptic inhibitory effect of TNF-α on the release of noradrenaline in isolated median eminence

Elenkov, Ilia J.; Kovács, Krisztina; Duda, E.; Stark, E.; Vizi, E. Sylvester

doi:10.1016/0165-5728(92)90203-w

Cited by 71 publications

(32 citation statements)

References 23 publications

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“…In contrast to the above excitatory effects of TNFα on central noradrenergic systems, TNFα inhibited NE release from the median eminence [97]. Similarly TNFα inhibited NE release from hippocampal slices [98].…”

Section: Tumor Necrosis Factor-αmentioning

confidence: 83%

Effects of cytokines and infections on brain neurochemistry

Dunn

2006

Clinical Neuroscience Research

282

169

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Administration of cytokines to animals can elicit many effects on the brain, particularly neuroendocrine and behavioral effects. Cytokine administration also alters neurotransmission, which may underlie these effects. The most well studied effect is the activation of the hypothalamopituitary-adrenocortical (HPA) axis, especially that by interleukin-1 (IL-1). Peripheral and central administration of IL-1 also induces norepinephrine (NE) release in the brain, most markedly in the hypothalamus. Small changes in brain dopamine (DA) are occasionally observed, but these effects are not regionally selective. IL-1 also increases brain concentrations of tryptophan, and the metabolism of serotonin (5-HT) throughout the brain in a regionally nonselective manner. Increases of tryptophan and 5-HT, but not NE, are also elicited by IL-6, which also activates the HPA axis, although it is much less potent in these respects than IL-1. IL-2 has modest effects on DA, NE and 5-HT. Like IL-6, tumor necrosis factor-α (TNFα) activates the HPA axis, but affects NE and tryptophan only at high doses. The interferons (IFN's) induce fever and HPA axis activation in man, but such effects are weak or absent in rodents. The reported effects of IFN's on brain catecholamines and serotonin have been very varied. However, interferon-γ, and to a lesser extent, interferon-α, have profound effects on the catabolism of tryptophan, effectively reducing its concentration in plasma, and may thus limit brain 5-HT synthesis.Administration of endotoxin (LPS) elicits responses similar to those of IL-1. Bacterial and viral infections induce HPA activation, and also increase brain NE and 5-HT metabolism and brain tryptophan. Typically, there is also behavioral depression. These effects are strikingly similar to those of IL-1, suggesting that IL-1 secretion, which accompanies many infections, may mediate these responses. Studies with IL-1 antagonists, support this possibility, although in most cases the antagonism is incomplete, suggesting the existence of multiple mechanisms. Because LPS is known to stimulate the secretion of IL-1, IL-6 and TNFα, it seems likely that these cytokines mediate at least some of the responses, but studies with antagonists indicate that there are multiple mechanisms. The neurochemical responses to cytokines are likely to underlie the endocrine and behavioral responses. The NE response to IL-1 appears to be instrumental in the HPA activation, but other mechanisms exist. Neither the noradrenergic nor the serotonergic systems appear to be involved in the major behavioral responses. The significance of the serotonin response is unknown.

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Section: Tumor Necrosis Factor-αmentioning

confidence: 83%

Effects of cytokines and infections on brain neurochemistry

Dunn

2006

Clinical Neuroscience Research

282

169

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“…This has been clearly demonstrated for the CNS through the hypothalamic-pituitary-adrenal axis and for the autonomic nervous system via an anatomic connection where nerve terminals end in peripheral immune organs (31,32). Immune cells have receptors for various neurotransmitters, neuropeptides, and hormones, and in turn, neural cells have receptors for cytokines (33,34). What has been much less clear is that molecules and signaling mechanisms used within the nervous system can be recapitulated in the immune system (35,36).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory role for GABA in autoimmune inflammation

Bhat¹,

Axtell²,

Mitra

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

415

381

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GABA, the principal inhibitory neurotransmitter in the adult brain, has a parallel inhibitory role in the immune system. We demonstrate that immune cells synthesize GABA and have the machinery for GABA catabolism. Antigen-presenting cells (APCs) express functional GABA receptors and respond electrophysiologically to GABA. Thus, the immune system harbors all of the necessary constituents for GABA signaling, and GABA itself may function as a paracrine or autocrine factor. These observations led us to ask further whether manipulation of the GABA pathway influences an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Increasing GABAergic activity ameliorates ongoing paralysis in EAE via inhibition of inflammation. GABAergic agents act directly on APCs, decreasing MAPK signals and diminishing subsequent adaptive inflammatory responses to myelin proteins.

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“…However, the neurochemical effects of TNF-␣ may depend upon the particular hypothalamic nuclei investigated. In fact, TNF-␣ was shown to dose-dependently inhibit electrically stimulated NE release from axon terminals of isolated rat median eminence and may act in a modulatory capacity with respect to CRH release from this site (Elenkov et al 1992).…”

Section: Central Neurochemical Variationsmentioning

confidence: 99%

Synergistic Effects of Interleukin-1β, Interleukin-6, and Tumor Necrosis Factor-α Central Monoamine, Corticosterone, and Behavioral Variations

Brebner

Hayley

Zacharko

et al. 2000

Neuropsychopharmacology

213

114

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The proinflammatory cytokines interleukin-1 ␤ (IL-1 ␤ ), IL-6, and tumor necrosis factor-alpha (TNF-␣ Dopamine; Monoamines; Neurochemical; Norepinephrine; Serotonin; Synergism; It is clear that interactions occur between the immune, endocrine, central, and autonomic nervous systems. Immunological manipulations (or products of an activated immune system, e.g., cytokines) may affect neuroendocrine and central neurotransmitter processes, and conversely, neuroendocrine and central neurotransmitter alterations may impact on immune activity (Blalock 1994;Dunn 1990;Rivier 1993;Rothwell et al. 1997). It has been posited that, among other things, the immune system acts like a sensory organ informing the brain of antigenic challenge (Blalock 1994) and that immune activation may be interpreted by the CNS as a stressor Dunn 1990). Further, cytokines may be part of a regulatory loop that, by virtue of effects on CNS functioning, might influence behavioral outputs and may even contribute to the symptoms of behavioral pathologies, including mood and anxietyrelated disorders . Indeed, in humans, depression was associated with variations of plasma cytokines, including interleukin-1 ␤ (IL-1 ␤ ), IL-1 receptor antagonist (IL-1Ra), IL-2, soluble IL-2 receptors, IL-6, and soluble IL-6 receptors Maes 1995;Maes et al. 1995;Muller and Ackenheil 1998).From the Institute of Neuroscience, Carleton University, Ottawa, Ontario, Canada (KB, SH, RZ, HA); and School of Psychology and Department of Cellular and Molecular Medicine (ZM), University of Ottawa, Ottawa, Ontario, Canada.Address correspondence to: Hymie Anisman, Ph.D., Life Sciences Research Building, Carleton University. Ottawa, Ontario K1S 5B6, Canada.Received January 28, 1999; revised May 10, 1999; accepted December 6, 1999. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 22 , NO . 6 Synergistic Effects of Cytokines 567Cytokines and bacterial endotoxins, such as lipopolysaccharide (LPS), induce a constellation of apparently adaptive behavioral changes, collectively referred to as "sickness behaviors" . For instance, these agents induce fever, reduce social exploration, sexual behaviors, and food consumption (Bluthe et al. 1992;Johnson et al. 1996;Plata-Salaman 1988;Plata-Salaman et al. 1988;O'Reilly et al. 1987). In addition, endotoxins may induce anxiogenic-like effects ) and disrupt responding for rewarding brain stimulation (Borowski et al. 1998), possibly reflecting anhedonic effects elicited by the immune challenge. The behavioral effects of endotoxin and cytokine treatment are paralleled by increased hypothalamic-pituitary-adrenal (HPA) activity, as reflected by increased activity of corticotropin releasing hormone (CRH) and elevated plasma ACTH and corticosterone levels (Kakucksa et al. 1993;Tilders et al. 1993). Inasmuch as cytokines elicit several effects similar to those of LPS, it has been assumed that at least some of the endotoxin effects involve IL-1 ␤ , or this cytokine acting conjointly or synergistically with IL-6 and/or TNF-␣ (Dunn 1992a; Ebisui et al. 1994;Long et...

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Presynaptic inhibitory effect of TNF-α on the release of noradrenaline in isolated median eminence

Cited by 71 publications

References 23 publications

Effects of cytokines and infections on brain neurochemistry

Effects of cytokines and infections on brain neurochemistry

Inhibitory role for GABA in autoimmune inflammation

Synergistic Effects of Interleukin-1β, Interleukin-6, and Tumor Necrosis Factor-α Central Monoamine, Corticosterone, and Behavioral Variations

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